STUDIES SHED LIGHT ON TESTOSTERONE REPLACEMENT THERAPY (TRT) EFFECTS
The TRAVERSE Study, a randomized controlled trial comparing TRT to placebo in hypogonadal men, found that TRT did not increase the risk of cardiovascular events over 33 months, albeit average treatment length was only 22 months and testosterone levels in the TRT group were below typical targets (median of 371 ng/dl). The large size of the trial (N=5246) made it a desirable setting to evaluate other TRT outcomes, spurring a number of recently published substudies. Findings from those analyses are summarized below.
- Erectile function and libido - TRT did not improve ED, while daily libido events (e.g., sexual activity, sexual thoughts, flirting, sexual daydreams, spontaneous erections), which had a baseline average of 1.8 per day in both groups, improved to 2.8 in the TRT group and 2.3 in the placebo group, yielding a difference of 0.47 that was statistically significant (p=0.011)
- Bone health - small studies have found that TRT increases BMD, so it was surprising that TRT-treated subjects had a significantly higher fracture risk over a median of 3.19 years (3.5% vs 2.46%, HR 1.43, 95%CI [1.04 to 1.97])
- Diabetes and insulin resistance - TRT did not reduce progression to diabetes among prediabetics, nor did it improve glucose control in diabetics
- Cognition, sleep, mood, energy - TRT had a modest but significant effect on mood and energy but no effect on cognition or sleep
- Prostate events - TRT did not increase the risk of prostate events (e.g., prostate cancer, acute urinary retention, prostate biopsy)
TRT proponents often tout it as a fountain of youth, and defining its true effects has been difficult, as past studies have been mostly small and heterogeneous. TRAVERSE helps close the knowledge gap and dispel some myths, but its short treatment duration and modest testosterone levels in the TRT group are significant weaknesses..
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"Wellbutrin DM" hits the market
A new antidepressant called Auvelity combines bupropion, a widely prescribed dopamine-norepinephrine reuptake inhibitor, with dextromethorphan, a cough suppressant that inhibits NMDA receptors. One caveat of the combination is that bupropion inhibits dextromethorphan's metabolism, increasing its exposure. Auvelity comes in one strength (dextromethorphan 45 mg/bupropion 105 mg), and maintenance dosing is one tablet twice daily. A very small 6-week study (N=87) found that it was superior to bupropion monotherapy for treating depression in adults. For those who are interested, GoodRx shows Auvelity costs more than $1000 for 60 tablets, while a one-month bupropion prescription and a bottle of dextromethorphan will set you back about $30.
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EFFECT OF NIRSEVIMAB (BEYFORTUS) ON RSV HOSPITALIZATIONS EVALUATED IN OPEN-LABEL TRIAL
Two prior studies found that nirsevimab, a monoclonal antibody against RSV virus, reduced symptomatic RSV infections by 6.9% in preterm infants (29 to <35 weeks gestation) and 3.8% in infants born ≥35 weeks. RSV hospitalizations, a secondary outcome, were reduced by 3.3% (p<0.001) and 1% (p=0.07), respectively. A third study using RSV hospitalization as the primary outcome was recently published. The HARMONIE trial randomized 8058 healthy infants born at ≥ 29 weeks gestational age (85% were born at ≥37 weeks) to nirsevimab or usual care before or during RSV season. At the end of the trial, RSV hospitalization occurred in 0.3% of nirsevimab-treated patients and 1.5% of the usual care group (p<0.001). Two infants in the nirsevimab group were admitted to the ICU compared to five in the usual care group. One patient in the usual care group was intubated, and no deaths occurred.
A major weakness of this study is its open-label design, as RSV hospitalization criteria were not standardized, and knowing the patient's nirsevimab status potentially swayed the admitting physician's decision. The authors were aware of this critique and tried to argue it away in a discussion that raised more questions than answers. Hard outcomes like ICU admission (7 patients) and mechanical ventilation (1 patient) were rare, as this was primarily a study in healthy term infants.
Collectively, these three studies show that nirsevimab reduces the severity of RSV infection, with infants born before 35 weeks receiving the greatest benefit. Its effect in healthy term infants is small and of questionable value. The CDC recommends all infants receive the shot, but these studies support prioritizing preterm infants, as 99% of term infants are fine without it. There was a shortage of nirsevimab during the height of last fall's RSV season, which means many preterm infants went without, thus showing the potential hazard of blanket recommendations that are common with the CDC.
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Combination inhaler with albuterol and budesonide available
Inhaled corticosteroids (ICS), short-acting beta agonists (SABA), and long-acting beta agonists (LABA) are the most commonly prescribed asthma treatments. Recent studies have found that as-needed ICS/LABA therapy is equal or superior to a daily ICS and as-needed SABA, contradicting traditional views that an ICS must be used daily to be effective. Recent GINA guidelines also recommend as-needed ICS/LABA therapy for most asthmatics. Keeping with the trend, Airsupra, the first inhaler to combine a SABA with an ICS, has been approved. It contains albuterol and budesonide and comes in a canister with 120 inhalations. Dosing is two puffs as needed with a max of 12 in 24 hours. It was superior to albuterol as a rescue inhaler in a double-blind study (N=3132) where participants were receiving maintenance ICS therapy.
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