Intravenous Iron Replacement Therapy In Eugonadal Males With Iron Deficiency Anemia (IDA): Effects On Pituitary Gonadal Axis and Sperm Parameters

Iron deficiency is one of the most common disorders affecting humans, and iron-deficiency anemia (IDA) continues to represent a major public health problem worldwide. There are an estimated 3.5 billion iron deficient people worldwide; the vast majority in developing countries Anemia imposes a significant hypoxic environment in different organs and tissues including the testes. Men and adult male animals produce a great amount of sperm every day, indicating that spermatogenesis in the seminiferous tubules of the testis occurs under a high proliferation rate, which demands considerable oxygen consumption. However, blood vessels are located exclusively between the tubules, and oxygen reaches the lumen of the seminiferous tubules only by diffusion. The seminiferous epithelium was speculated to operate on the verge of hypoxia because the testicular PO2 is relatively low, oxygen extraction is highly related to the metabolic demands of spermatogenesis, oxygen diffusion distance is comparatively long and the testis has little capacity to increase total blood flow

Aim of the study

To evaluate semen parameters and to assess serum FSH, LH, Testosterone (T) concentrations before and 6-7 weeks after intravenous iron therapy (800-1200 mg elemental iron therapy - IVI) in adults with iron deficiency anemia (IDA).

We studied 11 eugonadal adults with IDA , aged 40+/- 5 years, due to defective intake of iron. Anemia was diagnosed when haemoglobin (Hb) was equal or below 10g/dl. Serum iron, total iron binding capacity (TIBC) and ferritin concentrations confirmed the diagnosis of IDA. Basal serum concentrations of FSH, LH and T were measured.Semen parameters were evaluated before and 6-7 weeks after IVI therapy

After IVI therapy and correction of anemia, a significant increase of Hb from 8.1 ± 1.17 g/dL to 13.1 ± 0.7 g/dL was observed and was associated with an increase of T (from 12.22 ± 1.4 nmol/L to 15.9 ± 0.96 nmol/L; p < 0.001), FSH (from 2.82 +/- 0.87 to 3.82 +/- 1.08 IU/L; p = 0.007) and LH (from 2.27 +/- 0.9 to 3.82 +/- 1.5 IU/L; p =0.0002). Total sperm count (TSC) increased significantly from 72 +/- 17.5 million/ml to 158 ± 49 million/mL (p < 0.001), sperm volume increased from 2.3 +/- 0.6 ml to 2.6 +/- 0.7 ml (p = 0.045), rapid progressive sperm motility (RPM) increased from 22+/- 9.4 to 69 ± 30 million/ml (p < 0.001), and sperms with normal morphology (NM) increased from 33 +/- 5 to 56 +/- 7 million/ml (p < 0.001).

Increment in Hb concentration was correlated significantly with LH, FSH concentrations after IVI (r = 0.69 and r= 0.44 , r = 0.22 , respectively ; p< 0.01) and T concentrations (r = 0.75, p <0.001). The increment in serum T was correlated significantly with increments in the TSC and total sperm motility and RPM (r = 0.66, 0.43 and 0.55 respectively; p <0.001) but not with gonadotrophin levels.

Our study proved for the first time, to our knowledge , that correction of IDA with IVI is associated with significant enhancement of sperm parameters and increased concentrations of serum LH, FSH and T. These effects on spermatogenesis are reached by an unknown mechanism and suggest a number of pathways that need further human and/or experimental studies.

No relevant conflicts of interest to declare.