A combination therapy composed of a 5-alpha-reductase inhibitor and an alpha-blocker provides significant improvements in men with benign prostatic hyperplasia (BPH), according to a new study.
But a high percentage of patients discontinue the combo treatment due to several reasons, such as changing medication, improved lower urinary tract symptoms (LUTS) and choosing surgery to treat symptoms.
The study, “Long-Term Combination Therapy With Α-Blockers And 5α-Reductase Inhibitors In Benign Prostatic Hyperplasia: Patient Adherence And Causes Of Withdrawal From Medication,” was published in the International Neurourology Journal.
BPH treatments include alpha-blockers, or α-blockers, which have been shown to improve maximal flow rate and quality of life in patients, and inhibitors of the enzyme 5-alpha reductase (5ARIs), such as Propecia (finasteride) and Avodart (dutasteride), which reduce the total prostate volume and surgical risk in long-term follow-ups.
Combination therapy with both alpha-blockers and 5ARIs have been shown to be effective in reducing LUTS, decreasing the total prostate volume, and reducing the risk of disease progression compared to treatment with a single medication, and is therefore recommended for patients with moderate-to-severe LUTS and enlarged prostates.
But it was unknown whether the improvements caused by this combination are sustained over time.
To investigate the long-term therapeutic effects and patient adherence to combination therapy, researchers analyzed the medical records of 625 men with BPH (mean age of 73) receiving the combination therapy, with follow-ups for one to 12 years. Patients with neurological lesions, recurrent urinary tract infections, and prostate cancer were not included in the analysis.
Improvement was assessed at baseline (every six months for two years) and then each year by measuring several parameters, such as the International Prostatic Symptoms Score (IPSS), quality of life index, total prostate volume, maximal flow rate, voided volume, postvoid residual volume, and prostate-specific antigen (PSA) levels. Patients who died or did not refill their medication were considered to have dropped out from the follow-up analysis.
Researchers also identified why patients stopped taking the combination therapy by interviewing the participants. If medications were changed during the follow-up period, patients were grouped into the discontinued medication group.
Results showed that men with BPH taking a combination therapy (mean duration of 4.6 years) saw significant improvements in their condition. However, 360 patients (59 percent) discontinued the treatment, in which case the therapy had a mean duration of about two years.
The reasons men gave for discontinuing the combo treatment included a change in medication to a single therapy with alpha-blockers or antimuscarinics (124 patients, 19.8 percent); surgery (39 patients, 6.2 percent); and LUTS improvement (53 patients, 8.5 percent). Only 64 patients (10.2 percent) were considered lost to follow-up, and six (1.0 percent) stopped the combination therapy due to adverse side effects. A larger total prostate volume after short-term combination treatment was also a cause for withdrawal from combination therapy.
The authors conceded the study had limitations, including the absence of a placebo control group, the large loss in follow-up data, and the fact that all patients were recruited at the same hospital.
“Combination therapy of an α-1 blocker and 5ARI lead to significant improvements over baseline in LUTS, uroflowmetry parameters, and prostate variables over time,” the researchers wrote. “This was observed not only in the short-term but also over a long-term follow-up period of 12 years.”
“Changing medications, improved LUTS and choosing surgery are common reasons for discontinuing combination therapy. A larger [total prostate volume] after short-term combination treatment was among the factors that causes the withdrawal from combination therapy,” they wrote.