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

Abstract and Introduction

Abstract

Abnormal uterine bleeding in women with a blood dyscrasia, such as leukemia, or who experience thrombocytopenia secondary to myelosuppressive chemotherapy is a clinical condition associated with significant morbidity. Consequently, effective management is necessary to prevent adverse outcomes. Prevention of menorrhagia, defined as heavy regular menstrual cycles with more than 80 ml of blood loss/cycle or a cycle duration longer than 7 days, in this patient population is the goal of therapy. Gonadotropinreleasing hormone analogs (e.g., leuprolide) are promising therapies that have been shown to decrease vaginal bleeding during periods of thrombocytopenia and to have minimal adverse effects other than those associated with gonadal inhibition. In patients who experience menorrhagia despite preventive therapies, or in patients who have thrombocytopenia and menorrhagia at diagnosis, treatment is indicated. For these women, treatment options may include platelet transfusions, antifibrinolytic therapy (e.g., tranexamic acid), continuous high-dose oral contraceptives, cyclic progestins, or other therapies for more refractory patients such as danazol, desmopressin, and recombinant factor VIIa. Hormonal therapies are often the mainstay of therapy in women with menorrhagia secondary to thrombocytopenia, but data for these agents are sparse. The most robust data for the treatment of menorrhagia are for tranexamic acid. Most women receiving tranexamic acid in randomized trials experienced meaningful reductions in menstrual bleeding, and this translated into improved quality of life; however, these trials were not performed in patients with cancer. Further clinical trials are warranted to evaluate both preventive and therapeutic agents for menorrhagia in premenopausal women with cancer who are receiving myelosuppressive chemotherapy.

Introduction

Menstruation issues affect the quality of life of most women at some point during their lives and are a common reason for clinic visits to primary care physicians as well as gynecologists.[1–4] A cross-sectional study showed that almost 20% of over 20 million ambulatory care visits for gynecologic disorders over a 2-year period were attributable to menstruation issues.[5] The term abnormal uterine bleeding is used to define a change in a woman's menstrual cycle, the amount of blood loss, the duration of flow, or menses frequency.[6] The diagnosis and management of abnormal uterine bleeding can present a challenge to the clinician and, therefore, is a common reason for gynecologic referral.[7,8] Even after obtaining a complete medical history and patient evaluation, the underlying cause of abnormal uterine bleeding may not be clear due to its complexity.[9]

Abnormal uterine bleeding includes both noncyclic and cyclic uterine bleeding, with the most common type of noncyclic uterine bleeding being anovulatory bleeding.[10] Anovulatory bleeding is characterized by irregular bleeding that is often heavy. It is more routinely experienced by either adolescents or perimenopausal women. In contrast, ovulatory bleeding occurs more often than anovulatory bleeding, is cyclic, and is often associated with dysmenorrhea (painful menstruation).[7] Cyclic uterine bleeding that occurs at regular intervals and lasts for more than 7 days is referred to as menorrhagia.[9,10] Often, menorrhagia is defined by the quantity of blood lost rather than the duration of menses. The mean ± SD blood loss per normal menstrual cycle is 40 ± 20 ml, whereas menorrhagia is typically described as a loss of more than 80 ml/cycle.[6] Between 10–30% of menstruating women experience menorrhagia, with up to 50% of women encountering menorrhagia during the perimenopausal period.[11] In women with certain hemostatic disorders (e.g, von Willebrand's disease), 78–93% experience menorrhagia, whereas 50–75% of women with deficiencies in clotting factors report it.[12] Quality of life may be profoundly affected by menorrhagia, and one population-based study found that more than 50% of women reported refraining from social activities due to excessive menstruation.[3]

One major complicating factor that may hinder appropriate management of abnormal uterine bleeding, including menorrhagia, is the confusing and inconsistent historical terminology used in clinical practice to describe symptoms and signs of menstrual disorders. Reportedly, more than 20 terms meaning increased or heavy menstrual bleeding have been used in the medical literature over the past 100 year.[13] Table 1 includes some of the most common terms used in clinical practice to describe abnormal uterine bleeding.[1,8,13]

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