Does hereditary hemochromatosis (HH) affect men, women, or both?

From the Guidelines

Hereditary hemochromatosis (HH) affects both men and women, but men are about twice as likely to develop symptoms as women. This genetic disorder causes excessive iron absorption from food, leading to iron overload in various organs including the liver, heart, and pancreas. The natural history of disease due to hereditary hemochromatosis is not well understood but appears to vary considerably among individuals 1.

Key Points

• Men usually develop symptoms earlier and more severely than women, typically between ages 40-60, while women often develop symptoms after menopause, around age 50-60 1.
• The gender difference occurs primarily because women lose iron through menstruation, pregnancy, and childbirth, which provides some natural protection against iron accumulation until menopause.
• The most common form of HH is associated with mutations in the HFE gene, particularly the C282Y mutation, and follows an autosomal recessive inheritance pattern, meaning it can affect either gender when two copies of the mutated gene are inherited 1.
• Early detection through genetic testing and iron studies is important for both sexes, as treatment through regular phlebotomy (blood removal) can effectively manage iron levels and prevent organ damage in affected individuals regardless of gender 1.

Important Considerations

• Individuals with a family member, especially a sibling, who is known to have hereditary hemochromatosis may be more likely to develop symptoms and should be counseled regarding genotyping and further diagnostic testing as warranted 1.
• Therapeutic phlebotomy is the primary treatment for hemochromatosis, and treated individuals report inconsistent improvement of their signs and symptoms 1.

From the Research

Hereditary Hemochromatosis Affected Groups

• Hereditary hemochromatosis (HH) is an autosomal recessive disorder that affects both men and women 2, 3.
• The disease disrupts iron homeostasis, resulting in systemic iron overload, and can lead to various clinical manifestations, including liver, pancreas, joints, heart, skin, and pituitary gland involvement 2.
• Men have a 24-fold increased rate of iron-overload disease compared with women, and are often diagnosed earlier than women 3.
• Women are often diagnosed later than men, likely due to menstrual blood loss, which can delay the onset of symptoms 2.

Clinical Features and Diagnosis

• The clinical features of HH in women compared to men show that women can have full phenotypic expression of the disease, including cirrhosis 4.
• Women with HH tend to have lower serum ferritin levels and less iron removed by venesections compared to men 4.
• The diagnosis of HH requires confirmation of increased serum ferritin levels and transferrin saturation, with or without symptoms 3.
• Genetic testing for the HFE gene mutation can be performed in patients with elevated iron indices and a suspicion for hemochromatosis or liver disease 5.

Treatment and Management

• Treatment of HH typically involves phlebotomy to remove excess iron stores 2, 3, 5.
• Deferasirox, an iron chelator, has been shown to be effective in reducing iron burden in patients with HH who are refractory to or intolerant of phlebotomy 6.
• Dietary modification is generally unnecessary, and universal screening for HH is not recommended 3.