Good, and Safe, Results Tied to Oral Testosterone in Men With Deficiency

MIAMI — Oral testosterone replacement therapy (TRT) seemed safe and effective in men with testosterone deficiency, according to a meta-analysis.

Among nine studies that looked at changes in serum total testosterone, only men with testosterone deficiency who took an oral agent — predominantly testosterone undecanoate — saw a significant increase in total testosterone, with a mean change of 1.25 ng/mL (95% CI 0.22-2.29), reported Jake A. Miller, MD, of the University of California Irvine.

And in eight studies that recorded adverse effects, there was no statistically significant change in risk in patients taking oral testosterone versus placebo, with a risk ratio of -0.03 (95% CI -0.08 to 0.03), he said at the Sexual Medicine Society of North America (SMSNA) annual meeting.

Miller told MedPage Today that testosterone undecanoate was “not necessarily something that’s new. I just think that, unfortunately, it [oral testosterone in general] got stigmatized very early on, as far as its use, and now we’re starting to see that with the new formulation, we’re challenging some of those concerns.”

Earlier forms of oral testosterone, such as methyltestosterone, carried higher risks for liver toxicity, hypertension, and prostate enlargement because of its rapid metabolism. As a result, “multiple guidelines…essentially made a hard line to say ‘Do not use oral testosterone for these patients, just use injection, just use gel, just use intranasal’,” as these formulations are absorbed less rapidly, Miller said.

Three forms of oral undecanoate testosterone are currently FDA approved (Jatenzo, Tlando and Kyzatrex), and these could offer an alternative for patients who can’t use injectable, gel-based, or intranasal TRT.

The nine studies that compared oral testosterone to placebo had 606 patients and were done from 1989-2019, while the eight studies of adverse effects had 849 patients. The majority of patients were adult males with diagnosed testosterone deficiency, according to Miller. The meta-analysis excluded women and transgender patients who were taking oral testosterone, because these patients tended to take more than one form of testosterone.

Two studies reported very high incidences of adverse effects for both placebo and control groups, while five reported very low incidences of adverse effects for both groups. Miller said that was because of different criteria for what qualified as an adverse effect.

He said that “despite having some of this new data available, when they [guidelines] discuss oral testosterone, it’s clear based on the resources that they are only reviewing the data from the 1970s population, and excluding the more recent stuff. What we’re hoping to achieve with our paper is to say ‘Maybe we should start to re-evaluate now the new work [data] coming out.'”