Systemic Iron Deficiency in a Nonhuman Primate Model of Endometriosis

Abstract

Endometriosis is characterized by endometrial tissue development outside the uterus. Anemia and iron depletion do not commonly accompany endometriosis in women, despite chronic abdominal inflammation and heavy menstrual bleeding. The objective of this study was to examine iron kinetics associated with endometriosis by using a NHP model, to better understand the underlying mechanism of abnormal hematogram values in women with endometriosis. Hematologic data from 46 macaques with endometriosis were examined for signs of iron depletion. Bone marrow, liver, and serum were used to elucidate whether iron loss or inflammation best explained the hematologic findings. Additional serum markers and intestinal biopsies from NHP with and without endometriosis were evaluated for patterns in iron kinetics across the menstrual cycle and for relative dietary iron-absorbing capacity. Almost half of the NHP with endometriosis were anemic. Overall, NHP had decreased RBC counts, increased MCV, increased percentage of reticulocytes, decreased serum hepcidin, and decreased hepatic and bone marrow iron. Intestinal expression of ferroportin 1, a mediator of iron absorption, was increased, indicating that despite high dietary iron, intestinal iron absorption did not compensate for iron losses. We concluded that use of oral iron supplementation alone does not replenish iron stores in endometriosis. Consequently, iron stores should be evaluated in women with endometriosis, even without overt clinical signs of anemia.

Premenopausal Women With a Diagnosis of Endometriosis Have a Significantly Higher Prevalence of a Diagnosis or Symptoms Suggestive of Restless Leg Syndrome: A Prospective Cross-Sectional Questionnaire Study

“…For example, iron deficiency is an identified causative factor for RLS ( 19 ) and RLS symptoms are exacerbated with iron deficiency ( 25 ). Albeit limited, there is evidence suggesting that women with endometriosis have significantly decreased values of hematocrit, hemoglobin concentrations and mean cell volume compared with age-matched controls ( 26 ). In a non-human primate (macaques) model of spontaneously occurring endometriosis, surgical diagnosis of endometriosis were associated with a significant increased rates of iron deficiency anemia, lower systemic iron stores, and decreased serum iron levels ( 26 ).…”

“…Albeit limited, there is evidence suggesting that women with endometriosis have significantly decreased values of hematocrit, hemoglobin concentrations and mean cell volume compared with age-matched controls ( 26 ). In a non-human primate (macaques) model of spontaneously occurring endometriosis, surgical diagnosis of endometriosis were associated with a significant increased rates of iron deficiency anemia, lower systemic iron stores, and decreased serum iron levels ( 26 ). Furthermore, women with endometriosis commonly complain of symptoms such as fatigue and malaise ( 27 ), which may be linked to or exacerbated by, iron deficiency.…”

The Unmet Needs for Studying Chronic Pelvic/Visceral Pain Using Animal Models

“…Moreover, their endometrium and endometriosis tissues present mitochondrial impairment, which may be related to oxidative stress [ 155 ], a feature also observed in patients. As happens with some endometriosis patients, some macaques are anemic [ 156 ]. Furthermore, it is possible to find other species that spontaneously develop endometriosis in non-menstruating animals such as gorillas, horses, dogs, and guinea pigs, among others [ 157 , 158 , 159 ].…”

I Am the 1 in 10—What Should I Eat? A Research Review of Nutrition in Endometriosis

“…Iron-deficiency anemia is not often diagnosed in patients with EMS, despite heavy menstrual bleeding and chronic inflammation of the abdominal cavity. Atkins et al [73] examined non-human primate models (macaques) with and without endometriosis and observed anemia in almost half of the macaques with endometriosis and also an abnormal hematogram-decreased RBC counts and serum hepcidin and increased MCV and percentage of reticulocytes. Reduced levels of hepatic and bone marrow Fe were found and increased intestinal expression of ferroportin 1, a mediator of iron absorption, which indicates that though there was greater iron content in the diet, intestinal iron absorption did not equalize for the Fe loss.…”