Benign Prostatic Hyperplasia (BPH)
Benign prostatic hyperplasia (BPH) is a condition in which the prostate gland becomes enlarged. However, the actual size of the gland does not necessarily predict symptom severity. Some men with minimally enlarged prostate glands may experience symptoms while other men with much larger glands may have few symptoms. BPH is very common among older men, affecting about 60% of men over age 60 and 80% of men over age 80.
The symptoms associated with BPH are collectively called lower urinary tract symptoms (LUTS). These are generally classified as either voiding (obstructive) symptoms or storage (irritative) symptoms.
Common symptoms of BPH include:
Urinary retention (inability to void) is a serious symptom of severe BPH that requires immediate medical attention.
BPH is not a cancerous or precancerous condition. It rarely causes serious complications, and men usually have a choice whether to treat it immediately or delay treatment. Treatment options include medications and surgery. Five-alpha-reductase inhibitors (5-ARIs) and alpha-blockers are the main types of drugs used for BPH treatment.
In 2011, the FDA approved the widely used erectile dysfunction drug, tadalafil (Cialis) for treatment of BPH. Tadalafil may be used to treat BPH and erectile dysfunction in men who have both conditions. Tadalafil should not be used in combination with alpha-blockers or nitrate drugs.
Hyperplasia is a general medical term referring to an abnormal increase in cells. Benign prostatic hyperplasia (BPH) is noncancerous cell growth of the prostate gland. It is the most common noncancerous form of cell growth in men and usually begins with microscopic nodules in younger men. BPH is not a precancerous condition and does not lead to prostate cancer.
As BPH progresses, it can lead to enlargement of the prostate gland. About half of men with BPH go on to develop an actual overall increase in the size of the prostate. As BPH progresses, it can squeeze the urinary tube (urethra), causing urinary symptoms. These urinary difficulties are part of a group of symptoms called collectively lower urinary tract symptoms (LUTS).
About a third of men with BPH have LUTS symptoms that interfere with their quality of life. The size of the prostate gland does not necessarily relate to a patient’s symptoms. Not all men with BPH have LUTS, and not all men with LUTS have BPH.
Description of the Prostate Gland. The prostate is a walnut-shaped gland located below the bladder and in front of the rectum. It wraps around the urethra (the tube that carries urine through the penis).
Functions of the Prostate Gland. The prostate gland provides the following functions:
Changes During the Lifespan. The prostate gland undergoes many changes during the course of a man's life. At birth, the prostate is about the size of a pea. It grows only slightly until puberty, when it begins to enlarge rapidly. It reaches normal adult size and shape, about that of a walnut, when a man is in his early 20s. The gland generally remains stable until about the mid-40s, when, in most men, the prostate begins to grow again through a process of cell multiplication (hyperplasia).
The process of urination is complicated:
Doctors are not exactly sure what causes benign prostatic hyperplasia. The changes that occur with male sex hormone as part of the aging process appear to play a role in the enlargement of the prostate gland.
Male Hormones. Androgens (male hormones) affect prostate growth. The most important androgen is testosterone, which is produced in the testes throughout a man's lifetime. The prostate converts testosterone to another powerful androgen, dihydrotestosterone (DHT).
DHT stimulates cell growth in the tissue that lines the prostate gland (the glandular epithelium) and is the major cause of the rapid prostate enlargement that occurs between puberty and young adulthood. DHT is a prime suspect in prostate enlargement in later adulthood.
Female Hormones. The female hormone estrogen may also play a role in BPH. (Some estrogen is always present in men.) As men age, testosterone levels drop, and the proportion of estrogen increases, possibly triggering prostate growth.
Age is the major risk factor for BPH. Over half of men develop BPH by age 60 and about 85% of men have BPH by age 85. It is uncommon for BPH to cause symptoms before age 40.
A family history of BPH appears to increase a man's chance of developing the condition.
Some evidence indicates that the same risk factors associated with heart disease may increase the risk of developing BPH. These risk factors include obesity, high blood pressure, low levels of HDL (“good”) cholesterol, diabetes, and peripheral artery disease (PAD). Lifestyle factors that are unhealthy for the heart (such as lack of physical activity, cigarette smoking, and poor diet) may also possibly increase BPH risk or worsen its symptoms.
Lower urinary tract symptoms (LUTS) are categorized either as voiding (formerly called obstructive) or storage (formerly called irritative) symptoms. BPH is often, but not always, the cause of LUTS, especially the voiding symptoms. Other medical conditions, such as bladder problems, can also cause these symptoms.
Some men with BPH may have few or no symptoms. The size of the prostate does not determine symptom severity. An enlarged prostate may be accompanied by few symptoms, while severe LUTS may be present with normal or even small prostates.
Voiding symptoms can be caused by an obstruction in the urinary tract, which may be due to BPH. (Obstruction is the most serious complication of BPH and requires medical attention.) Voiding symptoms include:
Storage symptoms, also referred to as filling symptoms, include:
Urinary retention (inability to void) is a serious complication of severe BPH that requires immediate medical attention. Urinary retention can be a sign of obstruction in the bladder. Bladder obstruction can cause kidney damage, bladder stones, urinary tract infections, blood in the urine, and incontinence as urine dribbles out in small amounts.
A doctor makes a diagnosis of BPH based on description of symptoms, medical history, physical examination, and various blood and urine tests. If necessary, your doctor may refer you to a urologist for more complex test procedures.
Some diagnostic tests are used to rule out cancers of the prostate or bladder as the cause of symptoms. In some cases, symptoms of prostate cancer can be similar to those of BPH. Tests may also be performed to see if BPH has caused any kidney damage.
The doctor will ask about your personal and family medical history, including past and present medical conditions. The doctor will also ask about any medications you are taking that could cause urinary problems
Digital Rectal Exam. The digital rectal exam is used to detect an enlarged prostate. The doctor inserts a gloved and lubricated finger into the patient's rectum and feels the prostate to estimate its size and to detect nodules or tenderness. The exam is quick and painless. The test helps rule out prostate cancer or problems with the muscles in the rectum that might be causing symptoms, but it can underestimate the prostate's size. It is never the sole diagnostic tool for either BPH or prostate cancer.
Other Physical Examinations. The doctor will press and manipulate (palpate) the abdomen and sides to detect signs of kidney or bladder abnormalities. The doctor may test reflexes, sensations, and motor response in the lower body to rule out possible nerve-related (neurologic) causes of bladder dysfunction.
A PSA test measures the level of prostate-specific antigen (PSA) in the patient's blood. It is a widely used but controversial screening test for prostate cancer. High PSA levels may indicate prostate cancer, but BPH itself usually raises PSA levels. And, some drugs used to treat BPH can decrease PSA levels.
A urinalysis can detect signs of bleeding or infection. A urinalysis involves a physical and chemical examination of a urine sample. A urinalysis also helps rule out bladder cancer.
To determine whether the bladder is obstructed, an electronic test called uroflowmetry measures the speed of urine flow. To perform this test, the patient urinates into a special toilet equipped with a measuring device. A reduced flow may indicate BPH. However, bladder obstruction can also be caused by other conditions including weak bladder muscles and problems in the urethra.
Cystoscopy, also called urethrocystoscopy, is a test performed by a urologist to check for problems in the lower urinary tract, including the urethra and bladder. The doctor can determine the presence of structural problems including enlargement of the prostate, obstruction of the urethra or neck of the bladder, anatomical abnormalities, or bladder stones. The test may also identify bladder cancer, and causes of blood in the urine and infection.
In this procedure, a thin tube with a light at the end (cytoscope) is inserted into the bladder through the urethra. The doctor may insert tiny instruments through the cytoscope to take small tissue samples (biopsies). Cytoscopy is typically performed as an outpatient procedure. The patient may be given local, spinal, or general anesthesia.
Ultrasound is a painless procedure that can give an accurate picture of the size and shape of the prostate gland. Ultrasound may also be used for detecting kidney damage, tumors, and bladder stones. Ultrasound tests of the prostate generally use one of two methods:
The postvoid residual urine volume (PVR) test measures the amount of urine left after urination. Normally, about 50 mL or less of urine is left; more than 200 mL is a sign of abnormalities. Measurements in between require further tests. The most common method for measuring PVR is with a catheter, a soft tube that is inserted into the urethra within a few minutes of urination.
In addition to prostate cancer, other conditions and factors can cause lower urinary tract symptoms similar to those associated with BPH:
Because BPH rarely causes serious complications, men usually have a choice between treating it or opting for watchful waiting:
The choice between watchful waiting and treatment usually depends on symptom severity. The American Urological Association’s BPH Symptom Score uses seven questions to evaluate a patient’s urinary symptoms during the past month. (The International Prostate Symptoms Score is another index that is also used.) The questions are:
Responses for the first six questions are scaled from “not at all” to “almost always.” (The last question uses answers ranging from “none” to “5 or more times.”) Each response is assigned a number on a scale of 0 - 5 and totaled into a symptom score. The symptom score can fall anywhere between 0 and 35.
Patients with mild symptoms will have low scores and may decide to delay treatment. Higher scores indicate more severe symptoms. Treatment can reduce the score:
Your doctor can discuss with you the various treatment options and the likelihood of symptom relief they may provide. All treatments have various side effects, which need to be taken into consideration. Quality of life is as important as symptom severity.
Medications. In general, there is no reason to treat BPH with medications unless symptoms become very bothersome. The size of the prostate, determined by exam or ultrasound, cannot indicate the need for medications. Evidence suggests that:
Surgery. A quarter of men with moderate symptoms, and even more men with severe symptoms, eventually need surgery. If a man chooses surgery, there are many choices. Transurethral resection of the prostate (TURP) is the standard procedure, but less invasive procedures, particularly those using heat or lasers to destroy prostate tissue, are becoming more common.
The most common reason for choosing surgery is obstruction of the bladder outlet, which causes urinary retention. Surgery may also be a reasonable option when BPH is clearly related to one or more of the following conditions:
Increased urinary flow and reduced urine retention are the greatest improvements resulting from surgery. Often, however, the benefits of surgery are not permanent.
Certain lifestyle changes may help relieve symptoms and are particularly important for men who choose to avoid surgery or drug therapy. They include:
Decongestants and Antihistamines. Men with BPH should avoid, if possible, the many medications for colds and allergies that contain decongestants, such as pseudoephedrine (Sudafed, generic). Such drugs, known as adrenergics, can worsen urinary symptoms by preventing muscles in the prostate and bladder neck from relaxing to allow urine to flow freely. Antihistamines, such as diphenhydramine (Benadryl, generic), can also slow urine flow in some men with BPH.
Diuretics. Men who are taking diuretics (drugs that increase urination) may want to talk to their doctor about reducing the dosage or switching to another type of drug. Diuretics are important drugs for many people with high blood pressure, with a proven track record for saving lives. No one should go off these medications without medical supervision.
Other Drugs. Other drugs that may worsen symptoms are certain antidepressants and drugs used to treat spasticity.
Pelvic floor muscle exercises, first developed to help women with childbirth, may also help men prevent urine leakage, particularly after surgical procedures. These exercises strengthen the pelvic floor muscles that both support the bladder and close the sphincter.
Performing the Exercises. Since the muscle is internal and sometimes hard to isolate, doctors often recommend practicing while urinating:
A heart-healthy diet rich in vegetables and fruit may help reduce BPH risk. Some evidence indicates that fruits and vegetables rich in beta-carotene and vitamin C may help protect against BPH. Dietary choices should also focus on increasing intake of healthy fats, such as omega-3 fatty acids, and limiting intake of unhealthy saturated fats and trans-fatty acids.
Generally, manufacturers of herbal remedies and dietary supplements do not need approval from the FDA to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Patients should check with their doctor before using any herbal remedies or dietary supplements.
Popular herbal and dietary supplement treatments for BPH include:
The two main drug classes used for BPH are:
Because these two types of drugs work in different ways, combinations of the two may control symptoms in select patients more effectively than either drug alone. The combination treatment may work best for patients with larger prostate glands and higher PSA readings. Many men, however, can control their condition with a single drug.
Alpha-adrenergic antagonists, commonly called alpha-blockers, relax smooth muscles in the prostate and make it easier for urine to flow. They quickly improve symptoms, usually within days. Because these drugs are short-acting, symptoms return once a man stops taking the medication. Alpha-blockers do not shrink the size of the prostate or change PSA levels.
Alpha-blockers are generally referred to as either nonselective or selective:
Side Effects. Alpha-blockers can cause headache, and stuffy or runny nose. Alpha-blockers can reduce blood pressure, which may cause dizziness, lightheadedness, and fainting. Orthostatic hypotension, a sudden drop in blood pressure when standing, can occur and increases the risk of falling. Taking the medication close to bedtime can help reduce these side effects.
Because of the reduced blood pressure side effect, do not take non-selective alpha blockers with the phosphodiesterase (PDE5) inhibitors used for erectile dysfunction [sildenafil (Viagra), tadalafil (Cialis),vardenafil (Levitra), or avanafil (Stendra)]. Men who take selective alpha blockers may be able to use erectile dysfunction pills with guidance from a doctor. (Men may experience a decreased ejaculate while taking these drugs. However, erectile dysfunction is not a usual side effect of alpha-blockers, as it is with finasteride and dutasteride.)
A special concern for tamsulosin, and other selective alpha-blockers, is that they are associated with a condition called intraoperative floppy iris syndrome (IFIS). IFIS is a loss of muscle tone in the iris that can cause complications during cataract surgery. Patients who are planning cataract or other eye surgery should be sure to inform their doctors prior to the surgery. IFIS appears more likely to occur with selective alpha-blockers than non-selective alpha blockers.
The prostate gland contains an enzyme called 5 alpha-reductase that converts testosterone to another androgen called dihydrotestosterone. Drugs known as 5-alpha-reductase inhibitors (5-ARIs), block this enzyme and thus reduce dihydrotestosterone in the prostate thereby preventing prostate growth.
The 5-ARIs used for treating BPH are:
Because 5-ARIs help shrink enlarged prostates, they are most effective in reducing symptoms in men with very large prostates. These drugs take several months before they have an effect so men may not notice any signs of improvement for 3 - 6 months.
Side Effects. Finasteride and dutasteride can cause erectile dysfunction, lowered sexual drive (libido), and ejaculation and orgasm disorders. These drugs can reduce the volume and quality of semen released during ejaculation. These sexual side effects may sometimes persist even after the drug is discontinued. (A positive side effect of finasteride is possible reduction of hair loss related to male hormones and, in some cases, hair growth in men with mild-to-moderate male pattern baldness.)
These drugs decrease prostate-specific antigen (PSA) levels, which may mask the presence of prostate cancer. To resolve this problem, doctors calculate PSA levels in men taking these drugs by doubling the PSA values. This doubling equation helps provide an accurate measurement. The FDA advises doctors that an increase in PSA (even if it’s in a normal range) while taking this drug may indicate the presence of prostate cancer.
A matter of controversial debate is whether 5-ARIs help protect against prostate cancer. Some studies have suggested that 5-ARIs may lower a man’s risk for developing prostate cancer. However, based on other studies, the FDA advises that these drugs may actually increase the risk for being diagnosed with high-grade aggressive types of prostate cancer. At this time, 5-ARIs are not approved for prostate cancer prevention. Men who take these drugs for BPH should discuss this issue with their doctors. The FDA recommends that doctors rule out other urologic conditions, including prostate cancer, that may mimic BPH before prescribing 5-ARIs for BPH treatment.
Anticholinergic drugs, also called antimuscarinics, such as tolterodine (Detrol) may be helpful for some patients. For treatment of BPH, they may be prescribed either alone or in combination with an alpha-blocker drug.
Tadalafil (Cialis) is approved for treating BPH either alone or when it occurs along with erectile dysfunction. Tadalafil should not be used in combination with alpha-blockers without careful consideration and monitoring for excessive blood pressure lowering. Like all PDE5 inhibitor drugs used for erectile dysfunction, men who take nitrate drugs should not take tadalafil.
Several surgical approaches are used to treat BPH. Reasons for performing prostate surgery include:
Surgical options include invasive and minimally invasive procedures. The choice of which surgical procedure to use depends on various factors, including a man’s age and general health.
The most effective surgical procedure, transurethral resection of the prostate (TURP), is also the most invasive and has the highest risk for serious complications. However, because it is more effective than less invasive procedures, TURP remains the procedure of choice for many doctors.
Minimally invasive procedures use laser or some other form of heat to destroy excess prostate tissue. Although minimally invasive procedures may be an appropriate choice for some patients, including younger men, none to date have proven superior to TURP.
Transurethral resection of the prostate (TURP) involves surgical removal of the inner portion of the prostate, where BPH develops. It is the most common surgical procedure for BPH, although the number of procedures has dropped significantly over the past decades because of the increased use of effective medications.
Procedure. The surgeon inserts a fiber-optic endoscope, which is a thin tube, into the urethra. No incision or stitches are needed. The surgeon uses the endoscope to cut away excess prostatic tissue, and water solutions are used to flush away the excised matter. TURP usually requires a 1 - 2 day hospital stay.
A Foley catheter generally remains in place for 1 - 3 days after surgery to allow urination. This device is a tube inserted through the opening of the penis to drain the urine into a bag. The catheter can cause temporary bladder spasms that can be painful. The catheter may be removed while the patient is in the hospital or after he is sent home.
Recuperation. Urine flow is stronger almost immediately after most TURP procedures. After the catheter is removed, patients often feel some pain or sense of urgency as the urine passes over the surgical wound. These sensations generally last for about a week and then gradually subside. Complete healing takes about 2 months. The following are some tips for speeding recovery and avoiding complications:
Complications. The TURP procedure is generally safe but there are some risks for short- and long-term complications.
Immediate short-term complications after surgery may include:
Long-term complications after surgery may include:
Transurethral Incision of the Prostate (TUIP). In TUIP, the surgeon makes only one or two incisions in the prostate, causing the bladder neck and the prostate to spring open and reduce pressure on the urethra. TUIP is generally reserved for men with minimally enlarged prostates (30 grams or less) who have obstruction of the neck of the bladder.
TUIP is less invasive than TURP, has a lower rate of the same complications, particularly retrograde ejaculation, and usually does not require a hospital stay. More studies are still needed, however, to determine whether they are comparative in long-term effectiveness.
Open Prostatectomy. In open prostatectomy, the enlarged prostate is removed through an open incision in the abdomen using standard surgical techniques. This is major surgery and requires a hospital stay of several days. Open prostatectomy is used only for severe cases of BPH, when the prostate is severely enlarged, the bladder is damaged, or other serious problems exist. Some patients need a second operation because of scarring. Side effects of open prostatectomy can include erectile dysfunction and urinary incontinence.
Procedures. Laser technology is used for removal of prostate tissue. Laser procedures can usually be done on an outpatient basis, and there is little risk for bleeding. The procedure involves passing a small tube with a tiny camera and the laser fiber through the urethra of the penis. The procedure is performed under spinal, epidural, or general anesthesia.
Laser procedures have a faster recovery time and less risk of incontinence than invasive surgical procedures, but their long-term effectiveness is unclear. Laser surgery may not be appropriate for men with larger prostates. Different procedures are used to provide different degrees of thermal cell destruction that range from coagulation to complete vaporization:
These minimally invasive procedures carry fewer risks for incontinence or problems with sexual function than invasive procedures, but it is unclear how effective they are in the long term.
Transurethral Microwave Thermotherapy (TUMT). Transurethral microwave thermotherapy delivers heat using microwave pulses to destroy prostate tissue. A microwave antenna is inserted through the urethra with ultrasound used to position it accurately. The antenna is enclosed in a cooling tube to protect the lining of the urethra. Computer-generated microwaves pulse through the antenna to heat and destroy prostate tissue. When the temperature becomes too high, the computer shuts down the heat and resumes treatment when a safe level has been reached. The procedure takes 30 minutes to 2 hours, and the patient can go home immediately afterward.
Transurethral Needle Ablation (TUNA). Transurethral needle ablation is a relatively simple and safe procedure, using needles to deliver high-frequency radio waves to heat and destroy prostate tissue.
Transurethral Electrovaporization (TUVP). Transurethral electrovaporization uses high voltage electrical current delivered through a resectoscope to combine vaporization of prostate tissue and coagulation that seals the blood and lymph vessels around the area. Deprived of blood, the excess tissue dies and is sloughed off over time.
Prostatic stents used for BPH are flexible mesh tubes that are inserted into the urethra. Typically, the insertion procedure takes only 15 minutes. Patients need only regional anesthetic and mild sedation. There is minimal recuperation and no overnight hospital stay. Unfortunately, stents often need to be removed later because of poor placement or complications, including irritation when urinating, urinary tract infections, and treatment failure. At this point, stents seem best suited for high-risk surgical patients or those with a limited life expectancy.
Abrams P, Chapple C, Khoury S, Roehrborn C, de la Rosette J; International Scientific Committee. Evaluation and treatment of lower urinary tract symptoms in older men. J Urol. 2009 Apr;181(4):1779-87. Epub 2009 Feb 23.
Auffenberg GB, Helfand BT, McVary KT. Established medical therapy for benign prostatic hyperplasia. Urol Clin North Am. 2009 Nov;36(4):443-59, v-vi.
Barry MJ, Meleth S, Lee JY, Kreder KJ, Avins AL, Nickel JC, et al. Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial. JAMA. 2011 Sep 28;306(12):1344-51.
Bell CM, Hatch WV, Fischer HD, Cernat G, Paterson JM, Gruneir A, et al. Association between tamsulosin and serious ophthalmic adverse events in older men following cataract surgery. JAMA. 2009 May 20;301(19):1991-6.
Burke N, Whelan JP, Goeree L, Hopkins RB, Campbell K, Goeree R, et al. Systematic review and meta-analysis of transurethral resection of the prostate versus minimally invasive procedures for the treatment of benign prostatic obstruction. Urology. 2010 May;75(5):1015-22. Epub 2009 Oct 24.
Davidson JH, Chutka DS. Benign prostatic hyperplasia: treat or wait? J Fam Pract. 2008 Jul;57(7):454-63.
Donnell RF. Minimally invasive therapy of lower urinary tract symptoms. Urol Clin North Am. 2009 Nov;36(4):497-509, vi-vii.
Kramer BS, Hagerty KL, Justman S, Somerfield MR, Albertsen PC, Blot WJ,et al. Use of 5-alpha-reductase inhibitors for prostate cancer chemoprevention: American Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline. J Clin Oncol. 2009 Mar 20;27(9):1502-16. Epub 2009 Feb 24.
Lourenco T, Pickard R, Vale L, Grant A, Fraser C, MacLennan G, et al. Minimally invasive treatments for benign prostatic enlargement: systematic review of randomised controlled trials. BMJ. 2008 Oct 9;337:a1662. doi: 10.1136/bmj.a1662.
McVary KT, Roehrborn CG, Avins AL, Barry MJ, Bruskewitz RC, Donnell RF, et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011 May;185(5):1793-803. Epub 2011 Mar 21.
Moyad MA, Lowe FC. Educating patients about lifestyle modifications for prostate health. Am J Med. 2008 Aug;121(8 Suppl 2):S34-42.
Penson DF, Munro HM, Signorello LB, Blot WJ, Fowke JH; Urologic Diseases in America Project. Obesity, physical activity and lower urinary tract symptoms: results from the Southern Community Cohort Study. J Urol. 2011 Dec;186(6):2316-22. Epub 2011 Oct 20.
Roehrborn CG. Male lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Med Clin North Am. 2011 Jan;95(1):87-100.
Roehrborn CG, Siami P, Barkin J, Damião R, Major-Walker K, Morrill B, et al. The effects of dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the CombAT study. J Urol. 2008 Feb;179(2):616-21; discussion 621. Epub 2007 Dec 21.
Sarma AV, Wei JT. Clinical practice. Benign prostatic hyperplasia and lower urinary tract symptoms. N Engl J Med. 2012 Jul 19;367(3):248-57.
Tacklind J, Fink HA, Macdonald R, Rutks I, Wilt TJ. Finasteride for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2010 Oct 6;(10):CD006015.
Theoret MR, Ning YM, Zhang JJ, Justice R, Keegan P, Pazdur R. The risks and benefits of 5a-reductase inhibitors for prostate-cancer prevention. N Engl J Med. 2011 Jun 15. [Epub ahead of print].