Urinary and Sexual Dysfunction Prevalent in FAP Patients, Review Finds

Ana Pena, PhD avatar

by Ana Pena, PhD |

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Urinary and sexual problems are highly prevalent in people with familial amyloid polyneuropathy (FAP) and should be tackled by a comprehensive and multidisciplinary management plan to prevent further complications and improve quality of life, a review study contends.

The study, “Diagnosis and treatment of urinary and sexual dysfunction in hereditary TTR amyloidosis,” was published in the journal Clinical Autonomic Research.

Hereditary transthyretin amyloidosis (ATTR), also known as familial amyloid polyneuropathy (FAP), is a rare genetic disease caused by mutations in the transthyretin (TTR) gene. These mutations result in the build up of transthyretin proteins into amyloid fibrils that are deposited in nerves and other tissues. That can lead to progressive damage of organs, such as the heart, and to peripheral and autonomic neuropathy, or nerve diseases.

Some patients also are burdened with problems in the urinary tract, and with sexual dysfunction.

Due to its rarity and variable clinical signs, diagnosis of ATTR often is delayed. This can compromise treatment, since available therapy options are mainly effective at early disease stages, before tissue damage becomes irreversible.

Increased awareness in the medical community regarding such problems — in particular urinary and sexual issues — may improve early diagnosis.

Bearing this in mind, a team of researchers reviewed the current knowledge — including published studies, clinical trial results, and guidelines — on the prevalence, diagnosis, and management of urinary and sexual dysfunction in people with ATTR.

For the final analysis, the investigators selected a total of eight studies, whose data was further examined and compared.

The data showed that lower urinary tract symptoms, or LUTS — which refer to problems in the bladder, urethra, and prostate — were present in up to 83% of patients.

The most common symptoms were problems in voiding during urination, specifically hesitancy, straining, and intermittent stream, and urinary infections. Such infections were reported in up to 50% of patients. Problems voiding were reported in 34.8 to 87.5% of people in the studies.

Incomplete bladder emptying and accumulation of post-void residuals can lead to urinary infections. There then is a risk of the infection spreading to the upper parts of the urinary tract, including the kidneys or the ureters, which are the tubes that carry urine from the kidneys to the bladder.

Incontinence was observed in 16.7-37.5% of patients, and was mostly caused by a decline in urethral resistance. That resistance is generated by a bladder muscle, called the detrusor muscle, and forces urine into the urethra, which is the tube that conducts the urine out of the body.

To determine urinary tract problems in the ATTR population, the investigators recommended pressure flow urodynamic testing as a key diagnostic tool, in addition to comprehensive clinical examinations. Ideally, video-urodynamic testing — specifically a urodynamic test with fluoroscopic imaging — should be performed in patients with neurological involvement such as ATTR. Urinary tract imaging also may be helpful to rule out damage to the kidneys and ureters.

With urodynamic testing, the most common finding among people with ATTR is lower-than-normal activity of the detrusor muscle, found in 52.2−77.7% of patients. Another common problem, present in 18−71% of patients, is intrinsic sphincter deficiency, in which the urethral sphincter is unable to close properly to retain urine.

Many also had a reduced bladder sensation, and poor bladder compliance due to amyloid deposits on the bladder wall.

In the combination of studies, many people with the disease reported having difficulties during sexual activity. Men commonly reported erectile dysfunction, said to occur in over 40% of cases, and retrograde ejaculation.

The most common problems in women were sexual arousal disorder, or a lack of response to sexual stimulation, present in up to 72.5% of patients, and low sexual desire, reported in up to 39.2% of women. Many women also reported lack of vaginal lubrication (up to 68%), difficulty reaching orgasm (up to 62%), and painful intercourse, or dyspareunia (up to 39.2%).

The main therapies currently available for ATTR are liver transplant and tafamidis, medicines sold as the brand names Vyndaqel and Vyndamax. However, data regarding the benefits of these therapies for urinary and sexual problems are scarce.

Tafamidis has been approved since 2011 in Europe as an oral treatment for people with FAP. In the U.S., the medicine is approved for the treatment of heart disease in adults with wild-type or hereditary TTR cardiac amyloidosis, but not for the treatment for FAP.

Recent data suggests that tafamidis might lead to mild improvements in bladder sensation and contractility — the ability of the heart muscle to contract — and that liver transplantation may reduce urinary and sexual symptoms.

“Given the paucity of data in the ATTR population, treatment should be tailored to the individual patient,” the researchers said.

“The management of urinary and sexual dysfunction in patients with ATTR should ideally be multidisciplinary, involving urologists, neurologists, and physical medicine physicians, rehabilitation physicians, and physical and occupational therapists,” they added.

“The aims of this management should be to avoid upper urinary tract complications and to improve patients’ quality of life,” the researchers concluded.