Levonorgestrel intrauterine system effects on hemoglobin and serum ferritin among anemic women in Kenya

Introduction:

Anemia among women of reproductive age is a stubborn problem in resource-poor countries.  Approximately 38% and 41% of non-pregnant women in Africa and SE Asia, respectively, are anemic (1).  In the two regions combined, this sums to approximately 270 million cases.  At least half of anemia cases are due to iron deficiency.  Iron deficiency is estimated to be the cause of 18% of maternal deaths worldwide (2); a 10g/L increase in hemoglobin reduces maternal mortality by 29% (3).  Ministries of Health in many resource-poor countries have established programs such as iron supplementation, improving diets, and preventing infectious and communicable diseases that lead to anemia.  Still, the labor-intensive programs and interventions have limited reach and are thus ineffective for hundreds of millions of women.  Multi-prong approaches are needed (4).

The proposed study will take place in Nairobi, Kenya, which is a metropolis with more than three million inhabitants.  Nairobi has large slum areas with poor health conditions that are typical of many large capital cities in sub-Saharan Africa (5).  The national prevalence of anemia, iron-deficiency (corrected for inflammation), and iron-deficiency anemia among non-pregnant women in Kenya is 21.9%, 21.3%. and 14.0%, respectively (6).  In the lowest wealth quintiles of Kenyan society, characteristic of slum areas, the levels are 34.6%, 27.5%, and 20.8%, respectively.

The scientific premise for the proposed work is that a contraceptive technology (the levonorgestrel intrauterine system- LNG IUS) has been shown to reduce menstrual blood loss and consequently, increase hemoglobin and serum ferritin levels in broad populations of non-anemic women (7).  Given what is known about the delicate balance between intake of dietary iron, iron absorption, and iron losses from menstruation, it is highly plausible that retention of iron from using the LNG IUS can become another prong in the strategies to help alleviate anemia.  Both the US Centers for Disease Control and Prevention and the World Health Organization confirm that women with iron deficiency anemia can safely use the LNG IUS (Category 1 on Medical Eligibility Criteria) (8, 9). 

Objectives:

The primary objective is to compare hemoglobin changes over time in the randomized arms: LNG IUS versus a Combined oral contraceptives (COC) with ferrous fumarate tablets. The secondary objectives are (1) To compare serum ferritin changes over time in the randomized arms (2) To correlate changes in hemoglobin and serum ferritin to reported changes in menstrual blood loss (3) To assess and compare participants’ satisfaction with the two contraceptive products and (4) To monitor incidence of progression to severe anemia and compare randomized arms

Methods:

This randomized controlled trial will examine and compare changes in hemoglobin among anemic women randomized to either the LNG IUS or an LNG/EE/ferrous fumarate COC.  The equal-allocation, open label study will be conducted at a single site in Nairobi, Kenya.  The primary hypothesis that the mean change in hemoglobin in the group assigned to the LNG IUS will be superior to the COC/ferrous fumarate (control) group by at least 4 g/L after 18-months of product use.  The study products are approved for use only as contraceptives and are available in Kenya; this study is not seeking regulatory approval for a new indication. 

Clinic staff will recruit approximately 600 anemic women aged 18-50 who are seeking contraception and have regular menses.  Participation will require two low hemoglobin values (87 to 126 g/L, inclusive) taken approximately 2-4 weeks apart.  After randomization, each participant will be followed for 18 months; blood samples will be collected at enrollment and every six months for measuring hemoglobin, serum ferritin and other markers.  Intention-to-treat principles and per protocol analyses will be used to measure and compare mean change in hemoglobin (primary endpoint) and serum ferritin (secondary endpoint) in the randomized groups.  All results will be examined in relation to incidence of acute inflammation, changes in menstruation, and any non-study use of supplemental iron.

Utility: 

This study aims to determine whether the LNG IUS can raise hemoglobin and serum ferritin levels in a marginalized, anemic population