Overview 

Frey’s syndrome is a result of generic trauma or injury during surgical intervention or manipulation in the parotid region. The parotid region, which surrounds the parotid glands, are found on either side of the face and are closer to the ear than the nose. Injury to the auriculotemporal nerve interrupts the nervous signals sent to the parotid gland in the cheeks. As a result, the patient may experience severe sweating whilst thinking about food or drinks. Frey’s syndrome is commonly known to occur after the individual has undergone a parotidectomy (removal of the whole or part of the parotid gland). This article will look at the occurrence and management of Frey syndrome in patients of different genders. 

Common symptoms of this syndrome include excessive sweating around the cheeks, forehead and ears. Some cases have also been reported to have flushed appearance leading to warm skin in the areas mentioned above. These symptoms may arise several years after the surgery or trauma has taken place. Pain is also a symptom that some patients experience, though it is not very common.¹ 

Frey Syndrome is also called as:¹

• Baillarger’s syndrome
• Auriculotemporal syndrome
• Dupuy syndrome
• Gustatory sweating

Understanding and further analysing prevalence of Frey’s syndrome in different genders would make diagnosis and prognosis of the syndrome a lot simpler, making treatment more suited to the patient. This would significantly make patient management a lot more efficient, decreasing the number of affected patients.

Physiology of Frey’s syndrome  

Frey’s syndrome causes parasympathetic axons (axon in the neurons that carry signals to major organs) of the auriculotemporal nerve. This nerve extends from the forehead region to the cheeks and jaw region. Improper regeneration of the nerve fibers in the parotid regions causes different nerves to connect via different synapses. As a result of the mismatch between nerve fibers, different neurotransmitters are secreted across the synapse leading to an opposite stimulus being produced. In cases of the syndrome, the stimulus causes dilation of vessels.

Vessel dilation causes sweat glands to become stimulated. The sweat glands then produce excessive amounts of sweat.¹ 

Regeneration of the nervous tissue after parotidectomy usually takes around 6 to 8 months.²

Damaged sympathetic nerve fibers can also lead to excessive sweating caused by excessive acetylcholine neurotransmitter release from neighboring parasympathetic fibers. 

Factors that affect the development of the syndrome are:

• Undergoing a  parotidectomy
• Size and nature of the tumor
• Infection via neck surgery
• Trauma or accident 

Gender differences in Frey syndrome occurrence

A study showed that those assigned male at birth (AMAB)  are at a greater risk of having Frey's syndrome. The results of the study showed that people AMAB are 1.6 times more likely to develop the syndrome compared to those assigned female at birth (AFAB).³ 

Age is another factor that plays a key role in the development of the syndrome. The median age of patients who developed the syndrome was found to be 62 years. This could be as a result of older people undergoing more surgeries related to the face and neck. 

Apart from the difference in occurrence of Frey's syndrome after parotidectomy in people AMAB and AFAB, physiological differences between both genders can also cause the variation in occurrence. 

Biological differences between the two genders includes:⁴ 

• Sex chromosomes
• Epigenetics 
• Hormones 
• Nature of the immune system 
• Skin type including anatomy and function 

Other factors that affect the occurrence can include:⁴ 

• Diet 
• Exercise 
• Race and ethnicity 
• Lifestyle and habits 
• Exposure to radiation and sun  

Both factors play a role together which leads to the occurrence of the syndrome. 

Those AMAB have higher levels of sebum as compared to AFAB and hence sweat a greater amount. On the other hand, people AFAB have a greater tendency of vasodilation, so have increased blood supply and warmer, redder skin than AMAB. These observations can be seen when the symptoms arise in the patient. Although these are typical observations, not all patients may experience similar symptoms as they would vary according to the nature of the disease. 

Gender differences in treating and managing Frey’s syndrome

Prevention 

There are some techniques that have been widely discussed in order to prevent the syndrome from occurring. Some of them need to be done during surgery whereas others can be done before or after. 

Preventative techniques include adding thicker skin flaps using fat and connective tissues and also by adding protective layers for muscles. This prevents the parotid glands from getting disturbed so that they maintain their normal structure and function after the surgery is performed. Although each method of prevention has its own positives and drawbacks, the doctor and the preoperative team decide what sort of preventive technique must be used, if needed. 

It is important to note there does not seem to be a difference in the preventative measures taken based on the gender of the patient.¹ 

Treatment 

The most common treatment therapies include use of alcohol, antiperspirants and use of toxins which alter the nervous conduction in the nerves local to the parotid gland. 

• Scopolamine gel can also be applied topically to the area. The gel works on the principle of inhibiting the acetylcholine neurotransmitter at parasympathetic sites, which in turn reduces muscle contraction and reduces saliva production
• Botulinum toxin A (a toxin used for altering nervous conduction) effect seems to be statistically similar on both AMAB and AFAB. Although there are several other methodologies available for the treatment of Frey’s syndrome, this one remains the most widely and commonly used as it is commonly accessible and can be infected locally⁵ 
• Tympanic neurectomy, which includes removal of a nerve, can also be performed to help with Frey’s syndrome as the procedure shuts down parasympathetic activity and prevents excessive saliva from being produced

Discussion 

Frey’s syndrome does not appear to be gender specific, however people AMAB  do have a 1.6 times greater chance of developing it post parotidectomy.

Symptoms of the syndrome in people AFAB and AMAB  appear similar and there have seen very slight differences in type of symptoms by both genders. However, there are cases where other diseases or comorbidities influence the symptoms, making them seem less like typical Frey's syndrome symptoms. 

Management of the syndrome is very common for both the genders as the nature of most cases is similar to one another. However, advancements in gender sensitive diagnosis and treatment for this disease would be greatly beneficial for prognosis. It would also elevate the quality of personalised management of the syndrome, making it more patient focussed and improving the quality of life of the patient. 

As personalized medicine develops greatly, research on gender specific aspects of Frey's syndrome would also be researched into, along with biological differences such as the anatomy, physiology and neurological aspects which would increase the understanding of the syndrome.