Managing iron deficiency and anemia
Management of iron deficiency and iron deficiency anemia in the setting of HMB includes:
- workup for the etiology of the abnormal uterine bleeding (TABLE)
- reducing the source of blood loss, and
- iron supplementation to correct the iron deficiency state.
In most cases, workup, reduction, and repletion can occur simultaneously. The goal is not always complete cessation of menstrual bleeding; even short-term therapy can allow time to replenish iron storage. Use a shared decision-making process to assess what is important to the patient, and provide information about relative amounts of bleeding cessation that can be expected with various therapies.10
Treatment options
Medical treatments to decrease menstrual iron losses are recommended prior to proceeding with surgical interventions.11 Hormonal treatments are the most consistently recommended, with many guidelines citing the 52-mg levonorgestrel-releasing intrauterine device (LNG IUD) as first-line treatment due to its substantial reduction in the amount of bleeding, HMB treatment indication approved by the US Food and Drug Administration (FDA), and evidence of success in those with HMB.12
Any progestin or combined hormonal medication with estrogen and a progestin will result in an approximately 60% to 90% bleeding reduction, thus providing many effective options for blood loss while considering patient preferences for bleeding pattern, route of administration, and concomitant benefits. While only 1 oral product (estradiol valerate/dienogest) is FDA approved for managementof HMB, use of any of the commercially available contraceptive products will provide substantial benefit.11,13
Nonhormonal options, such as antifibrinolytics and nonsteroidal anti-inflammatory drugs (NSAIDs), tend to be listed as second-line therapies or for those who want to avoid hormonal medications. Antifibrinolytics, such as tranexamic acid, require frequent dosing of large pills and result in approximately 40% blood loss reduction, but they are a very successful and well-tolerated method for those seeking on-demand therapy.14 NSAIDs may result in a slight bleeding reduction, but they are far less effective than other therapies.15 Antifibrinolytics have a theoretical risk of thrombosis and a contraindication to use with hormonal contraceptives; therefore, concomitant use with estrogen-containing medications is reserved for patients with refractory heavy bleeding or for heavy bleeding days during the hormone-free interval, when benefits likely outweigh potential risk.16,17
Guidelines for medical management of acute HMB typically cite 3 small comparative studies with high-dose regimens of parenteral conjugated estrogen, combined ethinyl estradiol and progestin, or oral medroxyprogesterone acetate.18,19 Dosing recommendations for the oral medications include a loading dose followed by a taper regimen that is poorly tolerated and for which there is no evidence of superior effectiveness over the standard dose.20,21 In most cases, initiation of the preferred long-term hormonal medication plan will reduce bleeding significantly within 2 to 3 days. Many clinicians who commonly treat acute HMB prescribe norethindrone acetate 5 mg daily (up to 3 times daily, if needed) for effective and safe menstrual suppression.22
Iron replenishment: Dosing frequency, dietary iron, and multivitamins
Iron repletion is usually via the oral route unless surgery is imminent, anemia is severe, or the oral route is not tolerated or effective.23 Oral iron has substantial adverse effects that limit tolerance, including nausea, epigastric pain, diarrhea, and constipation. Fortunately, evidence supports lower oral iron doses than previously used.4
Iron homeostasis is controlled by the peptide hormone hepcidin, produced by the liver, which controls mobilization of iron from the gut and spleen and aids iron absorption from the diet and supplements.24 Hepcidin levels decrease in response to high circulating levels of iron, so the ideal iron repletion dose in iron-deficient nonanemic women was determined by assessing the dose response of hepcidin. Researchers compared iron 60 mg daily for 14 days versus every other day for 28 days and found that iron absorption was greater in the every-other-day group (21.8% vs 16.3%).25 They concluded that changing iron administration to 60 mg or more in a single dose every other day is most efficient in those with iron deficiency without anemia. Since study participants did not have anemia, research is pending on whether different strategies (such as daily dosing) are more effective for more severe cases. The bottom line is that conventional high-dose divided daily oral iron administration results in reduced iron bioavailability compared with alternate-day dosing.
Increasing dietary iron is insufficient to treat low iron storage, iron deficiency, and iron deficiency anemia. Likewise, multivitamins, which contain very little elemental iron, are not recommended for repletion. Any iron salt with 60 to 120 mg of elemental iron can be used (for examples, ferrous sulfate, ferrous gluconate).25 Once ingested, stomach and pancreatic acids release elemental iron from its bound form. For that reason, absorption may be improved by administering iron at least 1 hour before a meal and avoiding antacids, including milk. Meat proteins and ascorbic acid help maintain the soluble ferrous form and also aid absorption. Tea, coffee, and tannins prevent absorption when polyphenol compounds form an insoluble complex with iron (see box at end of article). Gastrointestinal adverse effects can be minimized by decreasing the dose and taking after meals, although with reduced efficacy.
Intravenous iron treatment raises hemoglobin levels significantly faster than oral administration but is limited by cost and availability, so it is reserved for individuals with a hemoglobin level less than 9 g/dL, prior gastrointestinal or bariatric surgery, imminent surgery, and intolerance, poor adherence, or nonresponse to oral iron therapy. Several approved formulations are available, all with equivalent effectiveness and similar safety profiles. Lower-dose formulations (such as iron sucrose) may require several infusions, but higher-dose intravenous iron products (ferric carboxymaltose, low-molecular weight iron dextran, etc) have a stable carbohydrate shell that inhibits free iron release and improves safety, allowing a single administration.26
Common adverse effects of intravenous iron treatment include a metallic taste and headache during administration. More serious adverse effects, such as hypotension, arthralgia, malaise, and nausea, are usually self-limited. With mild infusion reactions (1 in 200), the infusion can be stopped until symptoms improve and can be resumed at a slower rate.27
Continue to: The role of blood transfusion...