Cluster versus migraine headache: a gender split

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 Cluster headache is massively male preponderant (10:1). It is reputed to be the most painful of all headaches.  The throbbing pain is typically unilateral and is localized behind one of the eyes. As is the case for the vast majority of pathologies,  cluster headache has a hereditary component.  Immediate family members of affected individuals are 14 times more at risk for the condition than relatives of an unaffected person. There seem to be many aggravating factors (alcohol, cigarettes, allergy, orgasm, stress, brain lesions) but the most basic mechanism seems to be neurovascular inflammation of unknown origin. Because of the male preponderance, the effectiveness of cyproterone acetate, a synthetic steroid with antiandrogenic action, has been tested and has been found effective in lithium-resistant cases.  One conventional pharmacotherapy is lithium,  a non-specific serotonin agonist.   Curiously,  most relevant studies have shown that cluster headache male patients have low circulating testosterone, a finding compatible with the increasing incidence of the disease from adulthood to senescence.

Migraine is also a type of vascular headache,  more prevalent in women (4:1).  The throbbing pain is typically felt on one side of the back of the head.  The syndrome is four times more frequent than cluster headache.  There is a strong hereditary component.  The most common treatment seems to be GR43175, a serotonin agonist.  The unabbreviated name of this drug (3-(2-dimethylamino) ethyl-N-methyl-1H-indole-5-methane sulphonamide),  mercifully,  is not commonly used. Ergotamine, another serotonin agonist, is also effective.

There does not seem to be any articulated model apt to explain the sex difference in prevalence of these two pairs of very similar disorders.   Such models should be articulated as a contribution to our global understanding of the neurobiology of sex differences.  They could be of great help particularly in advancing our understanding of neurotransmitter dynamics which are different in men and women.

Another female-prevalent disorder is adductor spastic dysphonia  (ASD: 1.5:1).  These patients often experience a tremulous voice associated with evidence of an essential tremor (tremor related to action) elsewhere, including head, trunk and limbs. The mean age of onset in patients with ASD is around 45 years.  In about half the patients the onset is gradual (suggesting a neurodegenerative process).  However,  the remainder of the patients experience an abrupt onset, related to an upper respiratory tract infection, or, more often, to psychosocial stress. Factors which frequently result in a worsening of speech include stress, public speaking, tiredness, strong emotions, upper respiratory tract infections and prolonged use of the voice.  A few patients with severe symptoms undergo recurrent laryngeal nerve sectioning.  Another treatment for the most severe cases consists of local injections of botulinum toxin (Botox) bilaterally into the vocalis muscles.   My hunch as to why there is a .5% greater incidence of this disorder in women is simply that the precipitating factor of stress affects women more than men.   We will see in upcoming sections that women are more susceptible to developing personality disorders that are stress-related.

A vignette on a case of hysterical aphonia

McCue and McCue reported a case of hysterical aphonia in a 1988 issue of the American Journal of Clinical Hypnosis.   The patient was a 44 year old woman who,  shortly after onset of marital discord (loss of employment, violence, litigation, etc.),  had a panic attack on a bus,  lost consciousness and was hospitalized.   Upon awakening she could not move or speak.  Upon examination,   she was hyperventilating.  She soon recovered all her movements -except speech.    She understood what was said to her.   She expressed herself by writing,  gesticulating and drawing.   She was able to speak under hypnosis only.  As marital reconciliation progressed,  she recovered her speech,  though she occasionally stuttered.  She reported feeling very anxious.   Two and a half years later,  she had separated from her husband and was feeling much better and had no speech problem at all.

Though each sex is at risk for its own set of neurological problems,  overall,  the human male fetus seems to be at a slight disadvantage in face of any kind of diffuse physiological stressor:  such stressors include prematurity and low birth weight,  and various poisons.  In a study reported by June Reinisch, sex differences were analyzed in children whose mothers had taken barbiturates during pregancy.  Barbiturates reportedly have been prescribed in as many as 25% of pregnancies in the US and Europe over the last 30 years. Nevertheless, there are little if any data on long-term consequences of prenatal exposure to barbiturates in humans. Evidence from laboratory animals indicates that barbiturate exposure during early development results in abnormal neural and biochemical differentiation of the CNS, deficits in learning, retarded attainment of developmental milestones, alteration of behavioral and physiological sex differences, increased activity, and decreased responsiveness to aversive and appetitive stimuli. Barbiturates appear to influence the brain via 2 routes: by direct action on neural tissue and indirectly by altering hepatic metabolism of steroid hormones. In her study Reinisch concluded that prenatal exposure to barbiturates in human subjects may lead to learning disabilities, decreased IQ, performance deficits, increased incidence of psychosocial maladjustment, and demasculinization of gender identity and sex-role behavior in boys.