Testosterone Replacement Therapy to Combat Renal Failure?

A new review of existing research on hypogonadism suggested that testosterone replacement therapy can ameliorate the morbidity associated with renal failure in many men.

Experts from Boston University and Baylor College of Medicine searched for studies that measured both renal function and testosterone production. They found 6 with primary data and another 5 reviews that had collected relevant information.

A number of the studies found significant associations between renal failure and hypogonadism. The largest of them, a cross-sectional look at 260 patients with renal failure, found that only 23% of the men had normal levels of testosterone (>14 nmol/L), while 33% had levels between 10 nmol/L and 14 nmol/L and 44% had true testosterone deficiencies (<10 nmol/L).

The various studies identified several underlying reasons for the association between renal failure and hypogonadism. Renal failure typically reduces prolactin clearance, which inhibits the production of luteinizing hormone, which, in turn, reduces testosterone production. It also, in its later stages, could lead to uremia, which inhibits luteinizing hormone receptors in Leydig cells.

The medications used to treat renal failures make matters worse. Angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), spironolactone, ketoconazole, statins, and glucocorticoids are all thought to interfere with the synthesis of sex hormones.

Of course, renal failure also tends to reduce clearance rates for luteinizing hormone and follicle-stimulating hormone, which should tend to boost testosterone production. But that effect is either overwhelmed by the testosterone-reducing effects of renal failure or is somehow disrupted by renal failure, which certainly disrupts the feedback loop that typically signals the body to make more testosterone when levels fall low.

“Although, currently, all patients with renal failure are not screened for hypogonadism, certain findings support the adoption of this practice,” the study authors wrote in the Indian Journal of Urology.

Erectile dysfunction is very common among men with renal failure — one study found it in 87% of patients &mdash; but it did not necessarily indicate hypogonadism, since other aspects of the disease could trigger the problem.

In general, the onset of symptoms caused by hypogonadism tends to be very slow among patients with renal failure and those symptoms that do appear tend to be the non-specific sort that could easily stem from other sources: increased sleepiness, decreased energy and negative mood states.

Hypogonadism among men with renal failure may also increase mortality rates, particularly among men with end-stage renal disease. A recent study of 126 such men found that patients with testosterone levels between 8 nmol/L and 12 nmol/L had suffered more than twice as much cardiovascular disease as patients with testosterone levels above 12 nmol/L and that patients with testosterone levels below 8 nmol/L had suffered more than 3 times as much cardiovascular disease as patients with testosterone levels above 12 nmol/L.

These findings lead the study authors to conclude that physicians should take action.

“Given the potential benefits, testosterone therapy should be initiated in patients with clinical hypogonadism,” they wrote, noting that physicians should monitor patients closely for signs of negative effects.

“Different formulations of testosterone have been investigated in men with renal failure,” they continue. “Intramuscular injections of testosterone are associated with very variable serum levels, including significantly supratherapeutic levels initially and subtherapeutic levels prior to repeat dosing… For patients with renal failure, gels or pellets are likely to be safer given their steadier testosterone values with therapy.”