Familial Mediterranean Fever (FMF) is a genetic disorder characterized by recurrent episodes of fever and inflammation, primarily affecting people of Mediterranean descent. While it predominantly manifests with symptoms such as abdominal pain and joint swelling, recent studies have explored its association with erectile dysfunction in men.

What is “familial mediterranean fever”?

Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disorder characterized by recurrent episodes of fever, abdominal pain, chest pain, and joint inflammation. It primarily affects people of Mediterranean descent, hence the name. FMF typically begins in childhood but can occur at any age. The condition is caused by mutations in the MEFV gene, which encodes a protein called pyrin. Pyrin is involved in regulating inflammation, and mutations in the MEFV gene lead to abnormal activation of the body’s inflammatory response, resulting in the characteristic symptoms of FMF. While there is no cure for FMF, treatments such as colchicine can help manage symptoms and reduce the frequency and severity of flare-ups.

Links between FMF and ED

The exact mechanisms underlying ED in men with FMF are not fully understood, as research on this specific topic is limited. However, there are several potential mechanisms that could contribute to ED in individuals with FMF:

• Chronic Inflammation: FMF is characterized by recurrent episodes of inflammation, primarily in the abdomen and joints. Chronic inflammation can lead to endothelial dysfunction, which impairs the ability of blood vessels to dilate properly. Since adequate blood flow is essential for achieving and maintaining an erection, endothelial dysfunction caused by chronic inflammation may contribute to ED.
• Oxidative Stress: FMF is associated with increased levels of oxidative stress, which occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them with antioxidants. Oxidative stress can damage blood vessels and impair erectile function by affecting the nitric oxide pathway, which is essential for the relaxation of smooth muscle in the penis during sexual arousal.
• Psychological Factors: Living with a chronic condition like FMF can lead to psychological stress, anxiety, and depression, which are known risk factors for ED. The emotional burden of managing a chronic illness may negatively impact sexual function and contribute to ED in men with FMF.
• Medication Side Effects: Colchicine, which is commonly used to treat FMF, may have side effects that impact sexual function. While colchicine is generally well-tolerated, some individuals may experience adverse effects such as gastrointestinal symptoms or myopathy, which could indirectly affect sexual function.
• Direct Effects of Inflammation on Sexual Function: Inflammation in the pelvic region, either due to FMF-related inflammation or secondary to complications such as amyloidosis (a rare complication of FMF), could directly affect the nerves and blood vessels involved in achieving and maintaining an erection.

Diagnosis

Diagnosing ED in men with Familial FMF involves a comprehensive evaluation by a healthcare professional. Since FMF primarily manifests with symptoms such as recurrent fevers, abdominal pain, and joint inflammation, diagnosing FMF-induced ED may involve several steps:

Clinical History: The healthcare provider will take a detailed medical history, including any symptoms of FMF, the frequency and severity of febrile episodes, and the presence of other FMF-related complications such as amyloidosis.

Physical Examination: A physical examination may be conducted to assess for signs of FMF, such as abdominal tenderness or joint swelling, as well as to evaluate general health and any potential contributing factors to ED.

Laboratory Tests: Blood tests may be performed to assess for markers of inflammation, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Genetic testing may also be considered to confirm a diagnosis of FMF by identifying mutations in the MEFV gene.

Evaluation of Erectile Dysfunction: Various tests may be performed to evaluate erectile function, including:

• Questionnaires: Patients may be asked to complete validated questionnaires such as the International Index of Erectile Function (IIEF) to assess the severity and impact of ED on their sexual function.
  • Physical Examination: The healthcare provider may perform a genital examination to assess for any physical abnormalities or signs of vascular or neurological issues.
  • Laboratory Tests: Blood tests may be conducted to check for underlying conditions that could contribute to ED, such as diabetes, hormonal imbalances, or cardiovascular disease.
  • Vascular Studies: Tests such as penile Doppler ultrasound may be used to assess blood flow to the penis and detect any abnormalities in vascular function.
  • Psychological Assessment: Given the potential impact of psychological factors on ED, patients may undergo a psychological evaluation to assess for conditions such as anxiety or depression.

Multidisciplinary Approach: Since FMF-induced ED may involve both inflammatory and psychological factors, a multidisciplinary approach involving specialists such as rheumatologists, urologists, and mental health professionals may be beneficial in managing both FMF and ED effectively.

Treatment

Treating ED in men with FMF involves addressing both the underlying inflammatory condition and the symptoms of ED. Here are some treatment options that may be considered:

Management of FMF:

• Colchicine: Colchicine is the mainstay of treatment for FMF and is effective in reducing the frequency and severity of febrile episodes. By controlling inflammation, colchicine may indirectly improve endothelial function and alleviate ED symptoms in some individuals.
  • Biologic Agents: In cases where colchicine is insufficient or not tolerated, biologic agents such as interleukin-1 (IL-1) inhibitors (e.g., anakinra, canakinumab) may be used to control inflammation and prevent FMF flares. These medications have been shown to improve symptoms and quality of life in FMF patients and may have additional benefits for ED.
  • Lifestyle Modifications: Adopting a healthy lifestyle, including regular exercise, a balanced diet, stress management techniques, and smoking cessation, can help reduce inflammation and improve overall health, potentially benefiting both FMF and ED.

Treatment of Erectile Dysfunction:

• Oral Medications: Phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra), are commonly prescribed for ED. These medications enhance the effects of nitric oxide, a chemical that relaxes smooth muscles in the penis, leading to increased blood flow and improved erectile function.
  • Vacuum Erection Devices: Vacuum erection devices create a vacuum around the penis, drawing blood into the penis to facilitate an erection. This non-invasive treatment option may be suitable for some individuals with ED.
  • Penile Injections and Urethral Suppositories: Alprostadil, a prostaglandin E1 analogue, can be injected directly into the penis or inserted into the urethra to stimulate blood flow and induce an erection.
  • Penile Implants: For individuals with severe or refractory ED, surgical placement of a penile implant may be considered. Penile implants are devices that are surgically implanted into the penis to allow for on-demand erections.

Psychological Support:

• Counseling or therapy may be beneficial for individuals experiencing psychological factors contributing to ED, such as anxiety, depression, or stress related to living with a chronic condition like FMF.

Multidisciplinary Care:

• Collaboration between rheumatologists, urologists, sexual health specialists, and mental health professionals can help develop a comprehensive treatment plan tailored to the individual’s needs and preferences.

Summary

FMF, a genetic autoinflammatory disorder, has been associated with ED in men. The exact mechanisms are not fully understood, but chronic inflammation, oxidative stress, psychological factors, and medication side effects may play a role. Diagnosis involves a comprehensive evaluation, considering both FMF symptoms and ED. Treatment approaches include managing FMF with medications like colchicine and addressing ED with oral medications, devices, psychological support, and multidisciplinary care. Further research is needed to better understand the relationship between FMF and ED and to optimize treatment strategies for affected individuals.”

Emin ÖZBEK

Urologist

Istanbul- TURKIYE