Understanding dysautonomia and how it affects the urogenital tract

Dysautonomia is a collection of conditions characterised by dysfunction of the autonomic nervous system. The autonomic nervous system controls ‘automatic’ body functions like breathing, heart rate, blood pressure, pupil constriction in the eye, temperature, digestion and others.

In dysautonomia, these functions are dysregulated, resulting in symptoms such as feeling faint/fainting, lightheadedness, unstable blood pressure, abnormal heart rate, and digestive dysfunction, and if it is severe, dysautonomia may result in death (though this is rare).

Dysautonomia isn’t a disease in and of itself, but a disruption to the autonomic nervous system (ANS) that may occur for multiple reasons. For example, if the ANS is injured, dysautonomia can occur via several degenerative neurological diseases, be related to other medical conditions, or be a drug side effect.

In that sense, a dysautonomic state may occur in the person.

Who gets dysautonomia?

Anyone can have dysautonomia, with over 70 million people globally – of all ages, ethnicities and genders – diagnosed. Most people take a number of years to be diagnosed, with low dysautonomia literacy amongst practitioners, despite the high prevalence.

Dysautonomia can appear in conjunction with other conditions such as diabetes, multiple sclerosis, rheumatoid arthritis, celiac disease, Sjogren’s syndrome, lupus, and Parkinson’s disease.

Dysautonomia is also associated with hypermobile Ehlers-Danlos syndrome (hEDS), fibromyalgia, mast cell activation syndrome (MCAS)^1–3, small fibre neuropathy, fibromyalgia, migraines, chronic rhinitis, and chronic fatigue. Dysautonomia is also associated with long COVID⁴.

Forms of dysautonomia – POTS, NCS, MSA

Postural orthostatic tachycardia syndrome (POTS)
Neurocardiogenic syncope (NCS)
Multiple system atrophy (MSA)

What is postural orthostatic tachycardia syndrome (POTS)?

POTS is a condition whereby upon standing (‘orthostatic’), the heart rate increases (‘tachycardia’), and a person may feel lightheaded, faint, have chest pain or shortness of breath, gastrointestinal upset, shaking, exercise intolerance, sensitivity to hot or cold, and others.

POTS most often affects young women who are otherwise deemed well, and therefore POTS can be an invisible form of disability.

What is neurocardiogenic syncope (NCS)?

NCS is the most common form of dysautonomia, with, at its most mild, a couple of fainting spells across a lifetime. If NCS is severe, a person might faint several times per day, with the consequences of falls being broken bones, pain, bruising, strains, and sometimes brain injuries.

Day-to-day activities may be severely impacted and impeded – work, school and having a social life may become difficult, reducing quality of life and ability to advance financially, in education or build meaningful social connections.

Multiple system atrophy (MSA)

MSA is a rare neurodegenerative disorder with similarities to Parkinson’s disease, except that people with MSA are typically confined to bed within two years of diagnosis and die in 5 to 10 years.

Symptoms of dysautonomia

Tachycardia (improperly fast heart rate)
Bradycardia (improperly slow heart rate)
Poor blood flow to the heart, brain and other organs
Chest pains
Lightheadedness
Flushing
Fainting
Nausea
Fast or slow digestive transit time
Irritable bowel symptoms (diarrhoea, constipation, bloating)
Vaginal and urinary tract symptoms⁵
Menstrual irregularities
Blood pooling in the extremities
Shaking
Excessive or insufficient sweating
Cognitive impairments, brain fog
Headaches or migraines¹
Chronic fatigue
Chronic sinusitis or rhinusitis
Drug, food, and environmental intolerances
Histamine intolerance²

Dysautonomia, hormones, histamine and the bladder and vagina

There appear to be close links between dysautonomia and histamine.

Many with dysautonomia, mostly females, experience urinary tract issues^5–7. Histamine excess or sensitivity can result in bladder sensitivity^7–9, (‘overactive bladder’), resulting in frequency or urgency.

POTS is associated with hypermobile EDS (hEDS), mast cell activation syndrome (MCAS), histamine intolerance and the influence of female sex hormones¹⁰.

At My Vagina’s specialist clinic, we see a huge number of patients with vulvovaginal and bladder symptoms associated with histamine intolerance/excess. Particular symptoms include a sensation of burning in the vagina, bladder pressure, a diagnosis of vulvodynia or interstitial cystitis, and vaginal and urinary tract microbiome disturbances.

In some dysautonomias, there may be a lack of bladder sensation and motor function abnormalities, resulting in being unaware of a full bladder. This lack of awareness may cause overflow or stress urinary incontinence (involuntary leaking urine).

The menstrual cycle is closely linked with the cardiovascular system, while also being very inflammatory during both menstruation and ovulation. Those with POTS suffer from more menstrual issues, pelvic pain, vulval inflammation, and pain conditions associated with the vagina and vulva¹⁰. Vaginal prolapse is more common.¹⁰

Treatment for dysautonomia

Typical allopathic medical treatments for menstrual irregularities, bladder and vaginal symptoms involve suppressing the menstrual cycle hormonally, use of H1 and H2 antihistamine medications, and mast cell stabilisers.

My Vagina’s specialist clinical practitioners can provide 100% holistic support for people with dysautonomia who have distressing urogenital symptoms.

Most cardiovascular symptoms of dysautonomia can be resolved by lying down, which restores normal blood flow to the heart and chest. Obviously this doesn’t treat the underlying issue, only these specific symptoms. Treatment largely depends on what else is going on for the person, and supporting their health in as many ways as possible.

There is still a lot we don’t know about dysautonomia and why it happens.

Some people will improve over time, while others will not, and symptoms may worsen. Full recovery is possible, but it’s impossible to know who will get better and who will not. Management of symptoms may provide the best option for many.

Diagnostic delays are a very real problem since most doctors do not have any training in diagnosing or treating dysautonomia.

Diagnosis and treatment for POTS

Postural orthostatic tachycardia syndrome may mimic anaphylaxis – dizziness, low blood pressure, increased heart rate, flushing and hives or weals. POTS is associated with post-traumatic stress disorder (PTSD).

A tilt test is performed to diagnose POTS.

Familial dysautonomia^11,12 (Riley-Day syndrome)

Familial dysautonomia (FD) is a rare condition characterised by sensory and autonomic neuropathy due to a mutation in the ELP1 (IKBKAP) gene. Almost all FD patients report gastrointestinal symptoms and dysfunction, with research showing gut dysbiosis and an altered metabolome.

In a mouse model, the mice had reduced intestinal motility, which is also found in people with familial dysautonomia.

A functional ELP1 gene is required for the normal formation of the enteric nervous system (that operates the gut) but is also used in adulthood for regulating neuronal and non-neuronal cells and for specific innervation of the mucosa and intestinal smooth muscle.

Calcitonin gene-related peptide (CGRP) innervation was heavily reduced, alongside the lower number of dopaminergic neurons. Gastric biopsy shows reduced and disoriented axons in the mucosa.

In the mouse model, ELP1 was deleted exclusively from neurons, with significant changes to the colonic epithelium, with reduced E-cadherin expression, interrupted mucous layer organisation, and the infiltration of bacteria into the mucosa.

The deletion of ELP1 exclusively in neurons is enough to change the intestinal epithelium and interrupt the intestinal epithelial barrier. Neurons, therefore, play an important role in gastrointestinal epithelial integrity and homeostasis.

References^13,14

1.
Blitshteyn S. Dysautonomia, Hypermobility Spectrum Disorders and Mast Cell Activation Syndrome as Migraine Comorbidities. Curr Neurol Neurosci Rep. Published online October 17, 2023:769-776. doi:10.1007/s11910-023-01307-w
2.
Kohno R, Cannom DS, Olshansky B, et al. Mast Cell Activation Disorder and Postural Orthostatic Tachycardia Syndrome: A Clinical Association. JAHA. Published online September 7, 2021. doi:10.1161/jaha.121.021002
3.
Doherty TA, White AA. Postural orthostatic tachycardia syndrome and the potential role of mast cell activation. Autonomic Neuroscience. Published online December 2018:83-88. doi:10.1016/j.autneu.2018.05.001
4.
González-Alvarez F, Estañol B, González-Hermosillo JA, et al. Complete remission with histamine blocker in a patient with intractable hyperadrenergic postural orthostatic tachycardia syndrome secondary to long coronavirus disease syndrome. Journal of Hypertension. Published online March 8, 2024:928-932. doi:10.1097/hjh.0000000000003669
5.
Aubin MSt, Shridharani A, Barboi AC, et al. Lower urinary tract dysfunction in patients with dysautonomia. Clin Auton Res. Published online November 3, 2015:407-410. doi:10.1007/s10286-015-0320-z
6.
Sakakibara R, Hattori T, Uchiyama T, Asahina M, Yamanishi T. Micturitional disturbance in pure autonomic failure. Neurology. Published online January 25, 2000:499-499. doi:10.1212/wnl.54.2.499
7.
Kaufman MR, Chang‐Kit L, Raj SR, et al. Overactive bladder and autonomic dysfunction: Lower urinary tract symptoms in females with postural tachycardia syndrome. Neurourology and Urodynamics. Published online February 9, 2016:610-613. doi:10.1002/nau.22971
8.
Shan H, Zhang EW, Zhang P, et al. Differential expression of histamine receptors in the bladder wall tissues of patients with bladder pain syndrome/interstitial cystitis – significance in the responsiveness to antihistamine treatment and disease symptoms. BMC Urol. Published online November 12, 2019. doi:10.1186/s12894-019-0548-3
9.
Grundy L, Caldwell A, Garcia Caraballo S, et al. Histamine induces peripheral and central hypersensitivity to bladder distension via the histamine H₁receptor and TRPV1. American Journal of Physiology-Renal Physiology. Published online February 1, 2020:F298-F314. doi:10.1152/ajprenal.00435.2019
10.
Tailor V, Khullar V. Gynaecological Considerations in PoTS. Postural Tachycardia Syndrome. Published online October 21, 2020:141-152. doi:10.1007/978-3-030-54165-1_18
11.
Chaverra M, Cheney AM, Scheel A, et al. ELP1, the Gene Mutated in Familial Dysautonomia, Is Required for Normal Enteric Nervous System Development and Maintenance and for Gut Epithelium Homeostasis. J Neurosci. Published online August 13, 2024:e2253232024. doi:10.1523/jneurosci.2253-23.2024
12.
Axelrod FB. Familial dysautonomia. Muscle and Nerve. Published online February 17, 2004:352-363. doi:10.1002/mus.10499
13.
Conway AE, Verdi M, Shaker MS, et al. Beyond Confirmed Mast Cell Activation Syndrome: Approaching Patients With Dysautonomia and Related Conditions. The Journal of Allergy and Clinical Immunology: In Practice. Published online July 2024:1738-1750. doi:10.1016/j.jaip.2024.03.019
14.
Novak P. Autonomic Disorders. The American Journal of Medicine. Published online April 2019:420-436. doi:10.1016/j.amjmed.2018.09.027