Prostate Drugs Increase Risks of Falls, Fractures

Enlarged prostate, the hallmark of a condition known as benign prostatic hypertrophy or benign prostatic hyperplasia (BPH), is very common. The prostate gland enlarges in most men as they age. BPH rarely causes symptoms before age 40, but more than half of men in their 60s — and as many as 90 percent of men in their 70s and 80s — have some symptoms of BPH.[1]

A first-choice treatment for moderate to severe BPH is the family of medications known as alpha-blockers. A well-known side effect of these drugs, hypotension (low blood pressure) — typically upon standing — can lead to dizziness, fainting and falls. These adverse effects are less common with newer, second-generation alpha-blockers, which are designed to more selectively target the prostate. However, prior research has yielded mixed results regarding whether second-generation alpha-blockers increase the risk of fall- related injuries, such as fractures.

A recent study in The British Medical Journal (BMJ) reveals that second-generation alpha-blockers are associated with small increases in risks of falls, fractures and head trauma.[2] Therefore, patients starting these drugs should take precautions to minimize the risk of injury.

About BPH

The prostate is located below the bladder and encircles the urethra, the tube through which urine drains from the bladder. Symptoms of BPH arise from both prostate enlargement and undesirable increased prostate muscle tone.[3] These factors together impair urine flow from the bladder.

Common BPH symptoms involve changes or problems with urination, including:

• A hesitant, interrupted or weak stream
• Urgency (the sensation of needing to urinate immediately)
• Leaking and dribbling
• More frequent urination, especially at night

These symptoms initially are mild but gradually worsen over a period of years. In more severe cases, the bladder does not empty completely, increasing the risk for urinary tract infections (UTIs) and, in extreme cases, kidney damage.

Alpha-blockers

Five alpha-blockers have been approved by the Food and Drug Administration for treatment of BPH symptoms. Two older first-generation alpha-blockers — doxazosin (CARDURA) and terazosin — are also approved for treating hypertension (high blood pressure). (Public Citizen’s Health Research Group designates these older alpha-blockers as Do Not Use for hypertension because they are less effective than other drugs for lowering high blood pressure).

The other three alpha-blockers are known as second-generation alpha-blockers: alfuzosin (UROXATRAL), silodosin (RAPAFLO) and tamsulosin (FLOMAX, JALYN).

Alpha-blockers relieve the symptoms of BPH by relaxing muscles in the prostate. Overall, the five alpha-blockers appear to have similar effectiveness in relieving BPH symptoms.[4]

Alpha-blockers can cause hypotension by relaxing muscles in blood vessels that regulate blood pressure. However, second-generation alpha-blockers are much less potent in this regard.

A 2013 study showed that second-generation alpha-blockers are associated with a slightly increased risk of severe hypotension requiring hospitalization within eight weeks of starting the drug.[5] Some studies have suggested that this increased risk of hypotension with second-generation alpha-blockers translates into an increased risk of fall-related injuries,[6] but others suggest it does not.[7],[8]

The new BMJ study, published in October 2015, is the first study to assess injury risks in a large number of patients who were prescribed second-generation alpha-blockers for BPH.

The BMJ study[9]

Using detailed electronic medical and pharmacy records available for the more than 13 million people living in Ontario, the researchers identified all men over 65 who had received their first prescription for alfuzosin, silodosin or tamsulosin from 2003 to 2013 (approximately 147,000 patients).

They then compared these patients’ frequency of falls, fractures, head injuries and severe hypotension within 90 days of being prescribed the drug with an equal number of men with similar ages and health statuses who were not taking an alpha-blocker.

Of the study patients using an alpha-blocker, 84 percent were prescribed tamsulosin, 14 percent alfuzosin and 2 percent silodosin.

The researchers found that men prescribed a second-generation alpha-blocker had a 14 percent greater chance of going to the hospital for a fall and a 16 percent greater chance of suffering a new fracture than men not taking these drugs. Importantly, these outcomes appear to be related, as 80 percent of the men who sustained a fracture also had fallen.

The patients taking alpha-blockers also had a 15 percent higher risk of head trauma and an 80 percent greater risk of being seen in the emergency room or being hospitalized for hypotension than patients not exposed to these drugs.

It is important to recognize that the increased risks of these events were small. For example, the researchers estimated that approximately one additional patient experienced a fall per 600 patients treated with the drugs. Likewise, about one additional patient sustained a fracture per 1,700 patients, and one additional patient experienced head trauma per 1,250 patients prescribed these drugs.

The researchers concluded that health care providers and patients need to exercise caution when prescribing and taking second- generation alpha-blockers.

What You Can Do

If you develop BPH symptoms, you should see your health care provider to confirm the diagnosis and to rule out any complications, such as UTIs or kidney damage. If your symptoms are minimal, no treatment is necessary, no matter the size of your prostate. If the symptoms are bothersome and affect your quality of life, you should try conservative behavioral changes first (see box).

If behavioral changes fail to adequately address your symptoms, a second-generation alpha-blocker is the best choice for drug therapy. Be aware that the risk of hypotension, falls and related injuries is highest when first starting these drugs. These risks are increased when alpha-blockers are combined with hypertension drugs or nitrates.

To reduce the risks of hypotension and fall-related injuries, take alpha-blockers in the evening with food.[11] Try to have a companion stay with you for a few hours when you take your first dose. Do not drive or operate hazardous equipment until you know whether or not you become dizzy when using an alpha-blocker. Follow this advice especially for the 24 hours after the first dose, whenever a dose is increased or when resuming use after an interruption of therapy.

For the first several weeks after starting the drug, be alert for dizziness and be cautious when sitting up or standing. If you are lying down, hang your legs over the side of the bed for a few minutes, then get up slowly. When getting up from a chair, stay by the chair until you are sure that you are not dizzy, especially after the first dose. If you become dizzy, sit or lie down.

References

[1] Benign prostatic hypertrophy (BPH). WorstPills.org. /chapters/view/13. Accessed March 19, 2016.

[2] Welk B, McArthur E, Fraser LA, et al. The risk of fall and fracture with the initiation of a prostate-selective α antagonist: A population based cohort study. BMJ. 2015;351:h5398.

[3] Benign prostatic hypertrophy (BPH). WorstPills.org. /chapters/view/13. Accessed March 19, 2016.

[4] Cunningham GR, Kadmon D. Medical treatment of benign prostatic hyperplasia. UpToDate. Updated October 8, 2015. http://www.uptodate.com/contents/medical-treatment-of-benign-prostatic-hyperplasia?source=search_result&search=bph&selectedTitle=1~150. Accessed March 19, 2016.

[5] Bird ST, Delaney JAC, Brophy JM, et al. Tamsulosin treatment for benign prostatic hyperplasia and risk of severe hypotension in men aged 40-85 years in the United States: risk window analyses using between and within patient methodology. BMJ. 2013;347:f6320.

[6] Jacobsen SJ, Cheetham TC, Haque R, et al. Association between 5-alpha reductase inhibition and risk of hip fracture. JAMA. 2008;300:1660–1664.

[7] Souverein PC, Van Staa TP, Egberts ACG, et al. Use of alpha-blockers and the risk of hip/femur fractures. J Intern Med. 2003;254:548–554.

[8] Vestergaard P, Rejnmark L, Mosekilde L. Risk of fractures associated with treatment for benign prostate hyperplasia in men. Osteoporos Int. 2011;22:731–737.

[9] Welk B, McArthur E, Fraser LA, et al. The risk of fall and fracture with the initiation of a prostate-selective α antagonist: a population based cohort study. BMJ. 2015;351:h5398.

[10] Cunningham GR, Kadmon D. Medical treatment of benign prostatic hyperplasia. UpToDate. Updated October 8, 2015. http://www.uptodate.com/contents/medical-treatment-of-benign-prostatic-hyperplasia?source=search_result&search=bph&selectedTitle=1~150. Accessed March 19, 2016.

[11] Welk B, McArthur E, Fraser LA, et al. The risk of fall and fracture with the initiation of a prostate-selective α antagonist: a population based cohort study. BMJ. 2015;351:h5398.