The anti-inflammatory effects of 1-MNA are linked to its ability to stimulate endogenous PGI 2  secretion and reduce IL-4 and TNF-α levels. [ 12 ]  These effects are mediated by endothelial mechanisms rather than a direct impact on immune cell function, ensuring that the body’s immune response is not weakened. [ 13 ] [ 14 ]


1-MNA is an inhibitor of nicotinamide N-methyltransferase (NNMT). By inhibiting NNMT activity, it regulates NAD +  biosynthesis via the nicotinamide salvage pathway, the primary route for NAD +  synthesis in mammals. By participating in this pathway, 1-MNA optimizes NAD +  levels. [ 2 ]


Research published in  Nature Medicine  indicates that 1-MNA enhances SIRT1 expression and stability. [ 17 ]  SIRT1 is an enzyme associated with longevity.


Studies using the nematode  Caenorhabditis elegans  indicate that 1-MNA supplementation may extend lifespan. These studies also link 1-MNA to SIRT1. [ 18 ]


Animal experiments with diabetic rats have shown that 1-methylnicotinamide positively effects degenerative changes in the brain, allowing cognitive performance to be maintained longer. [ 19 ]  It also prevents depressive behavior with efficacy comparable to the common antidepressant fluoxetine. This effect is attributed to the reduction of neuroinflammation, pro-inflammatory cytokines (IL-6, TNF-α), and increased expression of BDNF (brain-derived neurotrophic factor), a protein supporting neuron survival and growth. [ 20 ]


The neuroprotective effects of 1-MNA involve shielding against neurotoxins, amyloid-beta plaques in the brain, neuroinflammatory responses, and neuronal apoptosis. It has been shown to improve memory deficits and cognitive functions, suggesting potential for treating neurodegenerative disorders. [ 15 ] [ 21 ]


1-MNA acts as a myokine, supporting the utilization of amino acids for gluconeogenesis in the liver and stimulating lipolysis in adipose tissue, thereby providing energy for muscles. [ 22 ]  Studies indicate that 1-MNA supplementation improves exercise tolerance and reduces fatigue. After one month of supplementation with 58 mg of 1-MNA, post-COVID-19 patients reported improved distances in a 6-minute walk test (6MWT), with 92% of participants experiencing better outcomes compared to controls. [ 16 ]


Additional studies highlight 1-MNA’s ability to enhance physical performance by stimulating PGI 2  release, protecting microcirculation, and ensuring adequate blood flow to muscle tissues. This mechanism may reduce cardiovascular risks associated with physical exertion, particularly in individuals with impaired endothelial response. [ 23 ]


1-MNA has been approved for use in food products in the form of 1-MNA chloride. The approval process in the European Union was successfully completed by PHARMENA SA. In 2017, the European Food Safety Authority (EFSA) confirmed the safety of 1-MNA chloride in food supplements, leading to its authorization in 2018 under EU Regulation 2018/1123. [ 24 ]


1-MNA chloride is currently used in dietary supplements. [ 25 ]  Other chemical forms of 1-MNA are not currently allowed on the market as food.


The safety of 1-MNA chloride has been thoroughly evaluated by EFSA, confirming its safe use. It must meet quality parameters defined in EU Regulation 2018/1123. [ 24 ] [ 26 ]


Nonoxynol-9 , sometimes abbreviated as  N-9 , is an  organic compound  that is used as a  surfactant .  It is a member of the   nonoxynol  family of nonionic surfactants.  N-9 and related compounds are ingredients in various cleaning and cosmetic products.  It is widely used in  contraceptives  for its spermicidal properties.


As a  spermicide , it attacks the  acrosomal  membranes of the  sperm , causing the sperm to be immobilized.
Nonoxynol-9 is the active ingredient in most spermicidal creams, jellies, foams, gel, film, and  suppositories . [ citation needed ]


Nonoxynol-9 is a common ingredient of most vaginal and anal lubricants due to its spermicidal properties.


A 2004 study found that over a six-month period, the  typical-use  failure rates for five nonoxynol-9  vaginal contraceptives  (film, suppository, and gels at three different concentrations) ranged from 10% to 20%. [ 2 ]


Many models of  condoms  are  lubricated  with solutions containing nonoxynol-9. In this role, it has been promoted as a backup method for avoiding pregnancy and a  microbicide for sexually transmitted diseases  in the event of condom failure. However, the 2001  WHO  /  CONRAD  Technical Consultation on Nonoxynol-9 concluded that:  There is no published scientific evidence that N-9-lubricated condoms provide any additional protection against pregnancy or STDs compared with condoms lubricated with other products.  Since adverse effects due to the addition of N-9 to condoms cannot be excluded, such condoms should no longer be promoted.  However, it is better to use N-9-lubricated condoms than no condoms. [ 3 ]


Compared to regular lubricated condoms, condoms containing nonoxynol-9 present another disadvantage — they are limited by the shelf-life of the
spermicide.  [ 4 ]


Almost all brands of  diaphragm  jelly contain nonoxynol-9 as the active ingredient.  This jelly may also be used for a  cervical cap . Most  contraceptive sponges  contain nonoxynol-9 as an active ingredient.


Nonoxynol-9 is sometimes included in shaving creams for its properties as a nonionic surfactant; it helps break down skin oils that normally protect hair from moisture, so that they become wet and, hence, softer and easier to shave.  Gillette  formerly used nonoxynol-9 for this purpose in its Foamy products, but has discontinued the practice.


Nonoxynol-9 is also found in  Bengay  Vanishing Scent as an inactive ingredient.


Nonoxynol-9 is also found in Zanfel poison ivy cream.  It effectively helps to break up the oil  urushiol  that causes the rash.


From 1996 to 2000, a  UN -sponsored study conducted in several locations in  Africa  followed nearly 1,000 sex workers who used nonoxynol-9 gels or a  placebo . The  HIV  infection rate among those using nonoxynol-9 was about 50% higher than those who used the placebo; those using nonoxynol-9 also had a higher incidence of  vaginal   lesions , which may have contributed to this increased risk. Whereas these results may not be directly applicable to lower-frequency use, these findings combined with lack of any demonstrated HIV-prevention benefit from nonoxynol-9 use led the  World Health Organization  to recommend that it no longer be used by those at high risk of HIV infection. The WHO further notes that "Nonoxynol-9 offers no protection against  sexually transmitted infections  such as  gonorrhoea ,  chlamydia ." [ 3 ]  A 2006 study of a nonoxynol-9 vaginal gel in female sex workers in  Africa  concluded that it did not prevent genital  human papillomavirus  (HPV) infection and could increase the virus's ability to infect or persist. [ 5 ]


Ormeloxifene , also known as  centchroman , is one of the  selective estrogen receptor modulators , [ 2 ]  or SERMs, a class of medication which acts on the  estrogen receptor . It is best known as a  nonsteroidal   oral contraceptive  which is taken once per week.  In India, ormeloxifene has been available as  birth control  since the early 1990s, and it was marketed there under the trade name  Saheli , [ 3 ]  currently available free-of-cost for the women in India as  Chhaya (Centchroman) . [ 4 ] [ 5 ]


Ormeloxifene has also been licensed under the trade names  Ormalin ,  Novex-DS ,  Centron , and  Sevista .


Ormeloxifene is primarily used as a contraceptive but may also be effective for  dysfunctional uterine bleeding  and advanced  breast cancer . [ 6 ]


Ormeloxifene may be used as a weekly oral contraceptive. [ 6 ]  The weekly schedule is an advantage for women who prefer an oral contraceptive, but find it difficult or impractical to adhere to a daily schedule required by other oral contraceptives.


For the first twelve weeks of use, it is advised to take the ormeloxifene pill twice per week. [ 6 ]  From the thirteenth week on, it is taken once per week. [ 6 ] [ 7 ]
The consensus is that backup protection in the first month is a cautious but sensible choice. A standard dose is 30 mg weekly, but 60 mg loading doses can reduce pregnancy rates by 38%. [ 8 ]


It has a failure rate of about 1-2% with ideal use which is slightly less effective than found for  combined oral contraceptive pills . [ 9 ]


There are concerns that ormeloxifene may cause  delayed menstruation . [ 12 ]


Ormeloxifene is a  selective estrogen receptor modulator  (SERM). In some parts of the body, its action is  estrogenic  (e.g.,  bones ), in other parts of the body, its action is  antiestrogenic  (e.g.,  uterus ,  breasts ). [ 13 ] [ 14 ] [ 15 ]  It causes an asynchrony in the  menstrual cycle  between  ovulation  and the development of the uterine lining, although its exact mode of action is not well defined. In clinical trials, it caused ovulation to occur later than it normally would in some women, [ 9 ]  but did not affect ovulation in the majority of women, while causing the lining of the uterus to build more slowly. It speeds the transport of any fertilized egg through the  fallopian tubes  more quickly than is normal. [ 9 ]  Presumably, this combination of effects creates an environment such that if fertilization occurs, implantation will not be possible. [ 9 ]


Ormeloxifene was first discovered by  Central Drug Research Institute (CDRI)  in  Lucknow , India. [ 13 ] [ 16 ]  Ormeloxifene was marketed in  Delhi  in July 1991 and in  India  in 1992, under the brand names  Saheli  and  Choice-7 . [ 9 ] [ 17 ]


Since 2018, Centchroman is provided free-of-cost to the women in India by the government under the brand name  Chhaya . [ 4 ] [ 18 ] [ 19 ] [ 20 ]


As of 2009, ormeloxifene was legally available only in India. [ 21 ]


Ormeloxifene has been tested and licensed as a form of birth control, as well as a treatment for dysfunctional uterine bleeding.


Spermicide  is a  contraceptive  substance that destroys  sperm , inserted vaginally prior to  intercourse  to prevent  pregnancy . As a contraceptive, spermicide may be used alone.  However, the pregnancy rate experienced by couples using only spermicide is higher than that of couples using other methods.  Usually, spermicides are combined with contraceptive  barrier methods  such as  diaphragms ,  condoms ,  cervical caps , and  sponges .  Combined methods are believed to result in lower pregnancy rates than either method alone. [ 2 ]


Spermicides are typically unscented, clear, unflavored, non-staining, and lubricative.


The most common active ingredient of spermicides is  nonoxynol-9 . Spermicides containing nonoxynol-9 are available in many forms, such as jelly (gel), films, and foams. Used alone, spermicides have a perfect use failure rate of 6% per year when used correctly and consistently, and 16% failure rate per year in typical use. [ 1 ]


This list of examples was provided by the Mayo Clinic: [ 3 ]


Nonoxynol-9  is the primary chemical in spermicides to inhibit sperm motility. Active secondary spermicidal ingredients can include  octoxynol-9 ,  benzalkonium chloride  and  menfegol . [ 4 ]  These secondary ingredients are not mainstream in the United States, where nonoxynol-9 alone is typical.  Preventing sperm motility will inhibit the sperm from travelling towards the egg moving down the fallopian tubes to the uterus. The deep proper insertion of spermicide should effectively block the cervix so that sperm cannot make it past the cervix to the uterus or the fallopian tubes.  A study observing the distribution of spermicide containing nonoxynol-9 in the vaginal tract showed “After 10 min the gel spread within the vaginal canal providing a contiguous covering of the epithelium of variable thickness.” [ 5 ]  The sole goal of spermicide is to prevent fertilization.


Menfegol is a spermicide manufactured as a foaming tablet. [ 6 ]  It is available only in Europe.


Octoxynol-9  was previously a common spermicide, but was removed from the U.S. market in 2002 after manufacturers failed to perform new studies required by the FDA. [ 7 ]


The spermicides  benzalkonium chloride  and sodium cholate are used in some  contraceptive sponges . [ 8 ]   Benzalkonium chloride might also be available in Canada as a suppository. [ 9 ]


The 2008  Ig Nobel Prize  (a  parody  of the  Nobel Prizes ) in Chemistry was awarded to Sheree Umpierre, Joseph Hill, and Deborah Anderson, for discovering that Coca-Cola is an effective spermicide, [ 10 ]  and to C.Y. Hong, C.C. Shieh, P. Wu, and B.N. Chiang for proving it is not. [ 11 ] [ 12 ]


Lemon juice solutions have been shown to immobilize sperm in the laboratory, [ 13 ]  as has Krest Bitter Lemon drink. [ 14 ]  While the authors of the Krest Bitter Lemon study suggested its use as a postcoital douche, this is unlikely to be effective, as sperm begin leaving the ejaculate (out of the reach of any douche) within 1.5 minutes of deposition.  No published studies appear to have been done on the effectiveness of lemon juice preparations in preventing pregnancy, though they are advocated by some as 'natural' spermicides. [ 15 ]


Lactic acid  preparations have also been shown to have some spermicidal effect, and commercial lactic acid-based spermicides are available. [ 16 ] [ 17 ]  A contraceptive containing  lactic acid, citric acid, and potassium bitartrate  (Phexxi) was approved for use in the United States in May 2020. [ 18 ]


Extractives of the  neem  plant such as  neem oil  have also been proposed as spermicides based on laboratory studies. [ 19 ]  Animal studies of creams and pessaries derived from neem have shown they have contraceptive effects; [ 20 ]  however, trials in humans to determine its effectiveness in preventing pregnancy have not yet been conducted.


Spermicides are believed to increase the contraceptive effectiveness of condoms. [ 2 ]


However, condoms that are spermicidally lubricated by the manufacturer have a shorter shelf life [ 21 ]  and may cause urinary tract infections in women. [ 22 ]  The  World Health Organization  says that spermicidally lubricated condoms should no longer be promoted.  However, they recommend using a nonoxynol-9 lubricated condom over no condom at all. [ 23 ]


Spermicides used alone are only about 91 percent effective. [ 24 ]   When spermicides are used in conjunction with condoms and other barrier methods there is a 97 percent effective rate for pregnancy prevention.


Temporary local skin irritation involving the vulva, vagina, or penis is the most common problem associated with spermicide use. [ 25 ]


Frequent use (two times or more a day) of  nonoxynol-9  containing spermicide is inadvisable if STI/HIV exposure is likely, because in this situation there is increased vulvovaginal epithelial disruption and increased risk of HIV acquisition. [ 25 ]


In 2007, the United States  Food and Drug Administration  (FDA) mandated that labels for nonoxynol-9  over-the-counter  (OTC) contraceptive products carry a new warning saying they do not protect against STDs and HIV/AIDS. [ 26 ] [ 27 ]


The first written record of spermicide use is found in the  Kahun Papyrus , an Egyptian document dating to 1850 BCE.  It described a  pessary  of crocodile dung and fermented dough. [ 28 ]   It is believed that the low  pH  of the dung may have had a spermicidal effect. [ 29 ]


Further formulations are found in the  Ebers Papyrus  from approximately 1500 BCE.  It recommended mixing seed wool, acacia, dates and honey, and placing the mixture in the vagina. It probably had some effectiveness, in part as a physical barrier due to the thick, sticky consistency, and also because of the  lactic acid  (a known spermicide) formed from the acacia. [ 29 ]


Writings by  Soranus , a 2nd-century Greek physician, contained formulations for a number of acidic concoctions claimed to be spermicidal.  His instructions were to soak wool in one of the mixtures, then place near the cervix. [ 28 ]


Laboratory testing of substances to see if they inhibited sperm motility began in the 1800s.  Modern spermicides nonoxynol-9 and menfegol were developed from this line of research. [ 28 ]  However, many other substances of dubious contraceptive value were also promoted.  Especially after the prohibition of contraception in the U.S. by the 1873  Comstock Act , spermicides—the most popular of which was  Lysol —were marketed only as "feminine hygiene" products and were not held to any standard of effectiveness.  Worse, many manufacturers recommended using the products as a  douche   after  intercourse, too late to affect all the sperm.  Medical estimates during the 1930s placed the pregnancy rate of women using many over-the-counter spermicides at seventy percent per year. [ 30 ]


A misconception about spermicides existed in the 1980s and 1990s. A 1988 literature review article noted that  in vitro  studies of nonoxynol-9 and other spermicides showed inactivation of STI pathogens, including HIV. [ 31 ]  But a 2002 systemic review and meta-analysis of nine randomized controlled trials of vaginal nonoxynol-9 for HIV and STI prevention involving more than 5,000 women (predominantly sex workers) found no statistically significant reduction in risk of HIV and STIs, but found a small statistically significant increase in genital lesions among nonoxynol-9 spermicide users. [ 32 ]  And in a high-risk population using a nonoxynol-9 vaginal gel more than three applications per day on average, the risk of HIV acquisition was increased. [ 25 ]


Currently available spermicides containing nonoxynol-9 are ineffective as microbicides, in particular as HIV-preventive measures. 17  Thus, spermicides used alone are not recommended to prevent HIV or other STIs. Furthermore, frequent use (more than 2 times a day) of spermicide causes more vulvovovaginal epithelial disruption, 18  which theoretically could increase susceptibility to HIV. In a high-risk population using a vaginal gel with nonoxynol-9 more than three applications per day on average, the risk of HIV acquisition was  increased  compared with placebo. 19


Disadvantages and cautions Local irritation Temporary skin irritation involving the vulva, vagina, or penis caused by either local toxicity or allergy to the formulation is the most common problem associated with spermicide use... Although vaginal epithelial disruption has been associated with frequent use (twice a day or more) of spermicides containing N-9, this is usually asymptomatic. In a low risk population, long-term use of N-9 containing methods was not associated with epithelial disruption. 22


N-9 spermicides are inadvisable if STI/HIV exposure is likely in situations that would involve frequent use defined as 2 times or more a day.


Vasopressin  infusions are in use for  septic shock  patients not responding to fluid resuscitation or infusions of  catecholamines  (e.g.,  dopamine  or  norepinephrine ) to increase the blood pressure while sparing the use of catecholamines. These argipressins have much shorter elimination half-life (around 20 minutes) than synthetic non-arginine vasopresines with much longer elimination half-life of many hours. Further, argipressins act on V1a, V1b, and V2 receptors which consequently lead to higher eGFR and lower vascular resistance in the lungs. A number of injectable arginine vasopressins are in clinical use in the United States and the European Union. Pitressin among others, is a  medication  most commonly used in the treatment of  frequent urination ,  increased thirst , and  dehydration  such as that resulting from  diabetes insipidus , which causes increased and diluted urine. [ 2 ] [ 3 ]  It is used to treat  abdominal distension  following some surgeries, and in  stomach roentgenography . [ 3 ]  Vasopressin is a hormone that affects the  kidneys  and reduces urine flow. [ 4 ]


Side effects may include  stomach ache ,  vertigo ,  pale skin ,  flatulence ,  headache , or  tremor . [ 3 ] [ 4 ]


It is available as a  generic medication . [ 5 ]


Vasopressin is used to manage anti-diuretic hormone deficiency. It has off-label uses and is used in the treatment of  gastrointestinal bleeding ,  ventricular tachycardia  and ventricular defibrillation. Vasopressin is used to treat diabetes insipidus related to low levels of  antidiuretic hormone . It is available as Pressyn. [ 6 ]


Vasopressin agonists are used therapeutically in various conditions, and its long-acting synthetic analogue  desmopressin  is used in conditions featuring low vasopressin secretion, as well as for control of bleeding (in some forms of  von Willebrand disease  and in mild  haemophilia A ) and in extreme cases of bedwetting by children.  Terlipressin  and related analogues are used as  vasoconstrictors  in certain conditions. Use of vasopressin analogues for  esophageal varices  commenced in 1970. [ 7 ]


Vasopressin infusions are also used as second line therapy in  septic shock  patients not responding to fluid resuscitation or infusions of  catecholamines  (e.g.,  dopamine  or  norepinephrine ).


Efficacy of vasopressin on systemic hemodynamics in catecholamine-resistant septic and postcardiotomy shock have been studied and published first in 2001 [ 8 ]  Later, the group concluded the ischemic skin lesions (ISL) developed in patients with catecholamine-resistant vasodilatory shock have multi-factorial cause and shall not necessarily been seen a side effect of AVP solely. The presence of septic shock and a history of peripheral arterial occlusive disease are independent risk factors for the development of ISL. [ 9 ]  In the last decade, in early hyperdynamic septic shock, the administration of high-dose AVP as a single agent proved to fail to increase mean arterial pressure in the first hour but maintains it above 70mmHg in two-thirds of patients at 48h. AVP decreases NE exposure, has no effect on the PrCO(2) - PaCO(2 )difference, and improves renal function and SOFA score. [ 10 ]  This led to development of a large trial to see theeffect of arginin vasopressin as add-on to norepinephrine in septic shock. [ 11 ]  It could be shown, if giving vasopressin in early stage of septic shock (norepinephrin < 15 microgramm/min and lactate < 1.4 mmol/L) there is a statistically significant interaction between vasopressin and corticosteroids. The combination of low-dose vasopressin and corticosteroids was associated with decreased 28 and 90 days mortality and organ dysfunction compared with norepinephrine and corticosteroids. [ 12 ]


The Surviving Sepsis Campaign guidelines recommend the very early management of the sepsis focusing on the hour-1 bundle. This includes use of Vasopressin 0.03 units/minute as add-on to norepinephrine (NE) with intent of either raising the  mean arterial pressure  or decreasing the norepinephrine dosage (i.e. de-catecholaminization). [ 13 ]


Modern interest in vasopressors as a treatment for cardiac arrest stem mostly from canine studies performed in the 1960s by anesthesiologists Dr. John W. Pearson and Dr. Joseph Stafford Redding in which they demonstrated improved outcomes with the use of adjunct intracardiac epinephrine injection during resuscitation attempts after induced cardiac arrest. [ 14 ]  Also contributing to the idea that vasopressors may be useful treatments in cardiac arrest are studies performed in the early to mid 1990s that found significantly higher levels of endogenous serum vasopressin in adults after successful resuscitation from out-of-hospital cardiac arrest compared to those who did not live. [ 15 ] [ 16 ]  Results of animal models have supported the use of either vasopressin or epinephrine in cardiac arrest resuscitation attempts, showing improved coronary perfusion pressure [ 17 ]  and overall improvement in short-term survival as well as neurological outcomes. [ 18 ]


Although both vasopressors, vasopressin and  epinephrine  differ in that vasopressin does not have direct effects on  cardiac contractility  as epinephrine does. [ 18 ]  Thus, vasopressin is theorized to be of increased benefit over epinephrine in cardiac arrest due to its properties of not increasing myocardial and cerebral oxygen demands. [ 18 ]  This idea has led to the advent of several studies searching for the presence of a clinical difference in benefit of these two treatment choices. Initial small studies demonstrated improved outcomes with vasopressin in comparison to epinephrine. [ 19 ]  However, subsequent studies have not all been in agreement. Several  randomized controlled trials  have been unable to reproduce positive results with vasopressin treatment in both  return of spontaneous circulation  (ROSC) and survival to hospital discharge, [ 19 ] [ 20 ] [ 21 ] [ 22 ]  including a  systematic review  and  meta-analysis  completed in 2005 that found no evidence of a significant difference with vasopressin in five studied outcomes. [ 17 ]


There is no current evidence of significant survival benefit with improved neurological outcomes in patients given combinations of both epinephrine and vasopressin during cardiac arrest. [ 17 ] [ 20 ] [ 23 ] [ 24 ]  A systematic review from 2008 did, however, find one study that showed a statistically significant improvement in ROSC and survival to hospital discharge with this combination treatment; unfortunately, those patients that survived to hospital discharge had overall poor outcomes and many sustained permanent, severe neurological damage. [ 22 ] [ 24 ]  A more recently published clinical trial out of Singapore has shown similar results, finding combination treatment to only improve the rate of survival to hospital admission, especially in the  subgroup analysis  of patients with longer "collapse to emergency department" arrival times of 15 to 45 minutes. [ 25 ]


Vasopressin  is used in managing hemodynamic instability in newborns and older children recovering from cardiac surgery. [ 26 ] [ 27 ] [ 28 ] [ 29 ] [ 30 ] [ 31 ]  There is evidence that some children recovering from cardiac surgery have relative vasopressin deficiency, such that their endogenous plasma concentrations of arginine vasopressin are lower than what would be expected in this clinical setting. [ 27 ] [ 28 ] [ 31 ]  Though low endogenous vasopressin concentrations in and of themselves do not cause hemodynamic instability, neonates and children recovering from cardiac surgery who develop hemodynamic instability and have low endogenous vasopressin concentrations are optimal candidates for this surgery.  Unfortunately, measurement of endogenous vasopressin concentration is time-consuming and cumbersome, and not practical for bedside application.  Copeptin, a more stable and easily measured product
of pro-AVP processing, may be a means of identifying patients with low endogenous vasopressin concentrations. [ 28 ]   Further research is needed. Also, systemic corticosteroids have been shown to suppress endogenous vasopressin production and release. [ 31 ]  Neonates and children recovering from cardiac surgery who are receiving systemic corticosteroid therapy may also be optimal candidates for vasopressin therapy should hemodynamic instability be present.


A  vasopressin receptor antagonist  is an agent that interferes with action at the  vasopressin receptors . They can be used in the treatment of  hyponatremia . [ 32 ]


The normal appearance of prostate is shown at high magnification. Note the small pink laminated concretion (these are corpora amylacea) in the gland lumen to the left of center. Note the infoldings of the columnar epithelium.The normal prostate is composed of glands and stroma. The glands are seen in cross section to be rounded to irregularly branching. These glands represent the terminal tubular portions of long tubuloalveolar glands that radiate from the urethra. The glands are lined by two cell layers: an outer low cuboidal layer and an inner layer of tall columnar mucin-secreting epithelium. These cells project inward as papillary projections. The fibromuscular stroma between the glands accounts for about half of the volume of the prostate. As a male ages, there are more likely to be small concretions within the glandular lumina, called corpora amylacea, that represent laminated condensations of prostatic secretions. The glands are normally separated by stroma. The prostate is surrounded by a thin layer of connective tissue that merges with surrounding soft tissues, including nerves. There is no distinct capsule.


The prostate "chips" seen here are the firm, rubbery fragments obtained from transurethral resection of prostate (TURP) performed for symptomatic nodular hyperplasia.Nodular prostatic hyperplasia (also termed benign prostatic hyperplasia, or BPH) is a common condition as men age. Perhaps a fourth of men have some degree of hyperplasia by the fifth decade of life. By the eighth decade, over 90% of males will have prostatic hyperplasia. However, in only a minority of cases (about 10%) will this hyperplasia be symptomatic and severe enough to require surgical or medical therapy. (Bushman, 2009). The mechanism for hyperplasia may be related to prostatic accumulation of dihydrotestosterone (DHT), formed from testosterone through the action of type 2 5α-reductase, an enzyme expressed mostly in stromal cells but not in prostatic epithelial cells. DHT binds to nuclear hormone receptors on both epithelial and stromal cells, stimulating growth. The effect of drugs which act to inhibit the enzyme 5-alpha reductase, which converts testosterone to dihydrotestosterone within cells. This blocks the growth-promoting androgenic effect and diminishes prostatic enlargement. Such drugs include finasteride and episteride. Drug therapy must be continued to remain effective. (Andríole et al, 2004). Another class of drugs used to treat BPH are the alpha 1-adrenoreceptors, including prazosin, alfuzosin, indoramin, terazosin, doxazosin, and tamsulosin. These alpha adrenergic blockers lead to relaxation of smooth muscle in prostate and help to relieve obstruction. Drug therapy must be continued to remain effective. (Auffenberg et al, 2009). The normal prostate weighs 20 to 30 gm, but most prostates with nodular hyperplasia can weigh from 50 to 100 gm. Hyperplasia begins in the region of the veru-montanum, in the inner zone of the prostate, and extends to involve lateral lobes. This enlargement impinges upon the prostatic urethra, leading to the difficulty on urination with hesitency that is typical for this condition. Dysuria, dribbling, and nocturia are also frequent. The urinary tract obstruction leads to urinary retention and risk for infection. In severe, prolonged cases, hydroureter with hydronephrosis and renal failure can ensue. (Wasserman, 2006). Microscopically, nodular prostatic hyperplasia consists of proliferating nodules of glands and intervening stroma. Most of the hyperplasia is contributed by glandular epithelial cell proliferation, but the stroma is also increased, and in rare cases may predominate. The glands may be more variably sized, with larger glands having more prominent papillary infoldings. Nodular hyperplasia is NOT a precursor to carcinoma. (Homma et al, 1996)


The gross appearance of adenocarcinoma of the prostate is shown here in cross section. The entire prostate is involved. The yellowish nodules represent larger foci of carcinoma.Adenocarcinoma of the prostate is common. It is the most common non-skin malignancy in elderly men. The prevalence of microscopic cancer may be 5% in men <30 years of age, and up to 59% by the age of 80 years . Many of these carcinomas remain small and clinically insignificant. However, some are not, and prostatic adenocarcinoma is second only to lung carcinoma as a cause for cancer-related deaths among men. (Bostwick et al, 2004) (Albertsen, 2020). Men with a higher likelihood of developing a prostate cancer (in the U.S.) include those of older age, black race, and family history. Those with an affected first-degree relative have a much greater risk. (Bostwick et al, 2004). Prostatic adenocarcinomas can be divided into two groups. The majority of these cancers are low-grade, indolent, and unlikely to cause death. Some prostate cancers are more aggressive, higher grade, and require treatment with systemic therapy for control. (Albertsen, 2020). Prostate cancers may be detected by digital examination, by magnetic resonance imaging, ultrasonography (transrectal ultrasound), or by screening with a blood test for prostate specific antigen (PSA). None of these methods can reliably detect all prostate cancers, particularly the small cancers. Widespread PSA screening is not cost-effective. Men whose life expectancy is less than 10 years may not pursue prostate cancer early detection because the likelihood of benefitis can be outweighed by the risk of harms from treatment. Men at higher risk for prostate cancer at earlier ages, including men of African ancestry or a family history of prostate cancer in nonelderly relatives, should be provided the opportunity for informed decision making at an earlier age than average-risk men. (Albertsen, 2020) (Van Poppel et al, 2021). American Cancer Society guidelines for prostate cancer screening indicate that "Men who have at least a 10-y life expectancy should have an opportunity to make an informed decision with their health care provider about whether to be screened for prostate cancer after receiving information about the potential benefits, risks, and uncertainties associated with prostate cancer screening; prostate cancer screening should not occur without an informed decision-making process." (Smith et al, 2019). PSA is a glycoprotein produced almost exclusively in the epithelium of the prostate gland. In the circulation PSA may be complexed to serum proteins or may be free (fPSA) and together comprise total PSA (tPSA). The tPSA is normally less than 4 ng/mL (normal ranges vary depending upon which assay is used). A mildly increased tPSA in a patient with a very large prostate can be due to nodular hyperplasia, or to prostatitis, rather than carcinoma. The fPSA correlates more closely with benign prostatic conditions than the tPSA. A rising tPSA is suspicious for prostatic carcinoma. Transrectal needle biopsy, often guided by ultrasound, is useful to confirm the diagnosis, although incidental carcinomas can be found in transurethral resections for nodular hyperplasia. (Jung et al, 2006). Prostatic adenocarcinomas are composed of small glands that are back-to-back, with little or no intervening stroma. Cytologic features of adenocarcinoma include enlarged round, hyperchromatic nuclei that have a single prominent nucleolus. Mitotic figures suggest carcinoma. Less differentiated carcinomas have fused glands called cribriform glands, as well as solid nests or sheets of tumor cells, and many tumors have two or more of these patterns. Prostatic adenocarcinomas almost always arise in the posterior outer zone of the prostate and are often multifocal. (Pearson et al, 1996). Prostatic adenocarcinomas are usually graded according to the Gleason grading system based on the pattern of growth. There are 5 grades (from 1 to 5) based upon the architectural patterns. Adenocarcinomas of the prostate are given two grade based on the most common and second most common architectural patterns. These two grades are added to get a final grade of 2 to 10. The stage is determined by the size and location of the cancer, whether it has invaded the prostatic capsule or seminal vesicle, and whether it has metastasized. (Gleason, 1992) (Epstein, 2010). The grade and the stage correlate well with each other and with the prognosis. The prognosis of prostatic adenocarcinoma varies widely with tumor stage and grade. Cancers with a Gleason score of <6 are generally low grade and not aggressive. Advanced prostatic adenocarcinomas typically cause urinary obstruction, metastasize to regional (pelvic) lymph nodes and to the bones, causing blastic metastases in most cases. Metastases to the lungs and liver are seen in a minority of cases.


This is a high grade, poorly differentiated adenocarcinoma of prostate. There is no gland formation, only single cells infiltrating through the stroma.Adenocarcinoma of the prostate is common. It is the most common non-skin malignancy in elderly men. The prevalence of microscopic cancer may be 5% in men <30 years of age, and up to 59% by the age of 80 years . Many of these carcinomas remain small and clinically insignificant. However, some are not, and prostatic adenocarcinoma is second only to lung carcinoma as a cause for cancer-related deaths among men. (Bostwick et al, 2004) (Albertsen, 2020). Men with a higher likelihood of developing a prostate cancer (in the U.S.) include those of older age, black race, and family history. Those with an affected first-degree relative have a much greater risk. (Bostwick et al, 2004). Prostatic adenocarcinomas can be divided into two groups. The majority of these cancers are low-grade, indolent, and unlikely to cause death. Some prostate cancers are more aggressive, higher grade, and require treatment with systemic therapy for control. (Albertsen, 2020). Prostate cancers may be detected by digital examination, by magnetic resonance imaging, ultrasonography (transrectal ultrasound), or by screening with a blood test for prostate specific antigen (PSA). None of these methods can reliably detect all prostate cancers, particularly the small cancers. Widespread PSA screening is not cost-effective. Men whose life expectancy is less than 10 years may not pursue prostate cancer early detection because the likelihood of benefitis can be outweighed by the risk of harms from treatment. Men at higher risk for prostate cancer at earlier ages, including men of African ancestry or a family history of prostate cancer in nonelderly relatives, should be provided the opportunity for informed decision making at an earlier age than average-risk men. (Albertsen, 2020) (Van Poppel et al, 2021). American Cancer Society guidelines for prostate cancer screening indicate that "Men who have at least a 10-y life expectancy should have an opportunity to make an informed decision with their health care provider about whether to be screened for prostate cancer after receiving information about the potential benefits, risks, and uncertainties associated with prostate cancer screening; prostate cancer screening should not occur without an informed decision-making process." (Smith et al, 2019). PSA is a glycoprotein produced almost exclusively in the epithelium of the prostate gland. In the circulation PSA may be complexed to serum proteins or may be free (fPSA) and together comprise total PSA (tPSA). The tPSA is normally less than 4 ng/mL (normal ranges vary depending upon which assay is used). A mildly increased tPSA in a patient with a very large prostate can be due to nodular hyperplasia, or to prostatitis, rather than carcinoma. The fPSA correlates more closely with benign prostatic conditions than the tPSA. A rising tPSA is suspicious for prostatic carcinoma. Transrectal needle biopsy, often guided by ultrasound, is useful to confirm the diagnosis, although incidental carcinomas can be found in transurethral resections for nodular hyperplasia. (Jung et al, 2006). Prostatic adenocarcinomas are composed of small glands that are back-to-back, with little or no intervening stroma. Cytologic features of adenocarcinoma include enlarged round, hyperchromatic nuclei that have a single prominent nucleolus. Mitotic figures suggest carcinoma. Less differentiated carcinomas have fused glands called cribriform glands, as well as solid nests or sheets of tumor cells, and many tumors have two or more of these patterns. Prostatic adenocarcinomas almost always arise in the posterior outer zone of the prostate and are often multifocal. (Pearson et al, 1996). Prostatic adenocarcinomas are usually graded according to the Gleason grading system based on the pattern of growth. There are 5 grades (from 1 to 5) based upon the architectural patterns. Adenocarcinomas of the prostate are given two grade based on the most common and second most common architectural patterns. These two grades are added to get a final grade of 2 to 10. The stage is determined by the size and location of the cancer, whether it has invaded the prostatic capsule or seminal vesicle, and whether it has metastasized. (Gleason, 1992) (Epstein, 2010). The grade and the stage correlate well with each other and with the prognosis. The prognosis of prostatic adenocarcinoma varies widely with tumor stage and grade. Cancers with a Gleason score of <6 are generally low grade and not aggressive. Advanced prostatic adenocarcinomas typically cause urinary obstruction, metastasize to regional (pelvic) lymph nodes and to the bones, causing blastic metastases in most cases. Metastases to the lungs and liver are seen in a minority of cases.


This is an immunohistochemical stain with antibody against prostate specific antigen. The cells of this prostatic adenocarcinoma exhibit positive staining.Adenocarcinoma of the prostate is common. It is the most common non-skin malignancy in elderly men. The prevalence of microscopic cancer may be 5% in men <30 years of age, and up to 59% by the age of 80 years . Many of these carcinomas remain small and clinically insignificant. However, some are not, and prostatic adenocarcinoma is second only to lung carcinoma as a cause for cancer-related deaths among men. (Bostwick et al, 2004) (Albertsen, 2020). Men with a higher likelihood of developing a prostate cancer (in the U.S.) include those of older age, black race, and family history. Those with an affected first-degree relative have a much greater risk. (Bostwick et al, 2004). Prostatic adenocarcinomas can be divided into two groups. The majority of these cancers are low-grade, indolent, and unlikely to cause death. Some prostate cancers are more aggressive, higher grade, and require treatment with systemic therapy for control. (Albertsen, 2020). Prostate cancers may be detected by digital examination, by magnetic resonance imaging, ultrasonography (transrectal ultrasound), or by screening with a blood test for prostate specific antigen (PSA). None of these methods can reliably detect all prostate cancers, particularly the small cancers. Widespread PSA screening is not cost-effective. Men whose life expectancy is less than 10 years may not pursue prostate cancer early detection because the likelihood of benefitis can be outweighed by the risk of harms from treatment. Men at higher risk for prostate cancer at earlier ages, including men of African ancestry or a family history of prostate cancer in nonelderly relatives, should be provided the opportunity for informed decision making at an earlier age than average-risk men. (Albertsen, 2020) (Van Poppel et al, 2021). American Cancer Society guidelines for prostate cancer screening indicate that "Men who have at least a 10-y life expectancy should have an opportunity to make an informed decision with their health care provider about whether to be screened for prostate cancer after receiving information about the potential benefits, risks, and uncertainties associated with prostate cancer screening; prostate cancer screening should not occur without an informed decision-making process." (Smith et al, 2019). PSA is a glycoprotein produced almost exclusively in the epithelium of the prostate gland. In the circulation PSA may be complexed to serum proteins or may be free (fPSA) and together comprise total PSA (tPSA). The tPSA is normally less than 4 ng/mL (normal ranges vary depending upon which assay is used). A mildly increased tPSA in a patient with a very large prostate can be due to nodular hyperplasia, or to prostatitis, rather than carcinoma. The fPSA correlates more closely with benign prostatic conditions than the tPSA. A rising tPSA is suspicious for prostatic carcinoma. Transrectal needle biopsy, often guided by ultrasound, is useful to confirm the diagnosis, although incidental carcinomas can be found in transurethral resections for nodular hyperplasia. (Jung et al, 2006). Prostatic adenocarcinomas are composed of small glands that are back-to-back, with little or no intervening stroma. Cytologic features of adenocarcinoma include enlarged round, hyperchromatic nuclei that have a single prominent nucleolus. Mitotic figures suggest carcinoma. Less differentiated carcinomas have fused glands called cribriform glands, as well as solid nests or sheets of tumor cells, and many tumors have two or more of these patterns. Prostatic adenocarcinomas almost always arise in the posterior outer zone of the prostate and are often multifocal. (Pearson et al, 1996). Prostatic adenocarcinomas are usually graded according to the Gleason grading system based on the pattern of growth. There are 5 grades (from 1 to 5) based upon the architectural patterns. Adenocarcinomas of the prostate are given two grade based on the most common and second most common architectural patterns. These two grades are added to get a final grade of 2 to 10. The stage is determined by the size and location of the cancer, whether it has invaded the prostatic capsule or seminal vesicle, and whether it has metastasized. (Gleason, 1992) (Epstein, 2010). The grade and the stage correlate well with each other and with the prognosis. The prognosis of prostatic adenocarcinoma varies widely with tumor stage and grade. Cancers with a Gleason score of <6 are generally low grade and not aggressive. Advanced prostatic adenocarcinomas typically cause urinary obstruction, metastasize to regional (pelvic) lymph nodes and to the bones, causing blastic metastases in most cases. Metastases to the lungs and liver are seen in a minority of cases.


Adenocarcinoma of the prostate is shown here at low power on the left, compared to benign prostate (in which glands contain corpora amylacea) at the right. Note how small and close-packed the neoplastic glands are.Adenocarcinoma of the prostate is common. It is the most common non-skin malignancy in elderly men. The prevalence of microscopic cancer may be 5% in men <30 years of age, and up to 59% by the age of 80 years . Many of these carcinomas remain small and clinically insignificant. However, some are not, and prostatic adenocarcinoma is second only to lung carcinoma as a cause for cancer-related deaths among men. (Bostwick et al, 2004) (Albertsen, 2020). Men with a higher likelihood of developing a prostate cancer (in the U.S.) include those of older age, black race, and family history. Those with an affected first-degree relative have a much greater risk. (Bostwick et al, 2004). Prostatic adenocarcinomas can be divided into two groups. The majority of these cancers are low-grade, indolent, and unlikely to cause death. Some prostate cancers are more aggressive, higher grade, and require treatment with systemic therapy for control. (Albertsen, 2020). Prostate cancers may be detected by digital examination, by magnetic resonance imaging, ultrasonography (transrectal ultrasound), or by screening with a blood test for prostate specific antigen (PSA). None of these methods can reliably detect all prostate cancers, particularly the small cancers. Widespread PSA screening is not cost-effective. Men whose life expectancy is less than 10 years may not pursue prostate cancer early detection because the likelihood of benefitis can be outweighed by the risk of harms from treatment. Men at higher risk for prostate cancer at earlier ages, including men of African ancestry or a family history of prostate cancer in nonelderly relatives, should be provided the opportunity for informed decision making at an earlier age than average-risk men. (Albertsen, 2020) (Van Poppel et al, 2021). American Cancer Society guidelines for prostate cancer screening indicate that "Men who have at least a 10-y life expectancy should have an opportunity to make an informed decision with their health care provider about whether to be screened for prostate cancer after receiving information about the potential benefits, risks, and uncertainties associated with prostate cancer screening; prostate cancer screening should not occur without an informed decision-making process." (Smith et al, 2019). PSA is a glycoprotein produced almost exclusively in the epithelium of the prostate gland. In the circulation PSA may be complexed to serum proteins or may be free (fPSA) and together comprise total PSA (tPSA). The tPSA is normally less than 4 ng/mL (normal ranges vary depending upon which assay is used). A mildly increased tPSA in a patient with a very large prostate can be due to nodular hyperplasia, or to prostatitis, rather than carcinoma. The fPSA correlates more closely with benign prostatic conditions than the tPSA. A rising tPSA is suspicious for prostatic carcinoma. Transrectal needle biopsy, often guided by ultrasound, is useful to confirm the diagnosis, although incidental carcinomas can be found in transurethral resections for nodular hyperplasia. (Jung et al, 2006). Prostatic adenocarcinomas are composed of small glands that are back-to-back, with little or no intervening stroma. Cytologic features of adenocarcinoma include enlarged round, hyperchromatic nuclei that have a single prominent nucleolus. Mitotic figures suggest carcinoma. Less differentiated carcinomas have fused glands called cribriform glands, as well as solid nests or sheets of tumor cells, and many tumors have two or more of these patterns. Prostatic adenocarcinomas almost always arise in the posterior outer zone of the prostate and are often multifocal. (Pearson et al, 1996). Prostatic adenocarcinomas are usually graded according to the Gleason grading system based on the pattern of growth. There are 5 grades (from 1 to 5) based upon the architectural patterns. Adenocarcinomas of the prostate are given two grade based on the most common and second most common architectural patterns. These two grades are added to get a final grade of 2 to 10. The stage is determined by the size and location of the cancer, whether it has invaded the prostatic capsule or seminal vesicle, and whether it has metastasized. (Gleason, 1992) (Epstein, 2010). The grade and the stage correlate well with each other and with the prognosis. The prognosis of prostatic adenocarcinoma varies widely with tumor stage and grade. Cancers with a Gleason score of <6 are generally low grade and not aggressive. Advanced prostatic adenocarcinomas typically cause urinary obstruction, metastasize to regional (pelvic) lymph nodes and to the bones, causing blastic metastases in most cases. Metastases to the lungs and liver are seen in a minority of cases.


This is a high grade adenocarcinoma of prostate with single infiltrating cells. A residula normal prostatic gland is seen at the left of center.Adenocarcinoma of the prostate is common. It is the most common non-skin malignancy in elderly men. The prevalence of microscopic cancer may be 5% in men <30 years of age, and up to 59% by the age of 80 years . Many of these carcinomas remain small and clinically insignificant. However, some are not, and prostatic adenocarcinoma is second only to lung carcinoma as a cause for cancer-related deaths among men. (Bostwick et al, 2004) (Albertsen, 2020). Men with a higher likelihood of developing a prostate cancer (in the U.S.) include those of older age, black race, and family history. Those with an affected first-degree relative have a much greater risk. (Bostwick et al, 2004). Prostatic adenocarcinomas can be divided into two groups. The majority of these cancers are low-grade, indolent, and unlikely to cause death. Some prostate cancers are more aggressive, higher grade, and require treatment with systemic therapy for control. (Albertsen, 2020). Prostate cancers may be detected by digital examination, by magnetic resonance imaging, ultrasonography (transrectal ultrasound), or by screening with a blood test for prostate specific antigen (PSA). None of these methods can reliably detect all prostate cancers, particularly the small cancers. Widespread PSA screening is not cost-effective. Men whose life expectancy is less than 10 years may not pursue prostate cancer early detection because the likelihood of benefitis can be outweighed by the risk of harms from treatment. Men at higher risk for prostate cancer at earlier ages, including men of African ancestry or a family history of prostate cancer in nonelderly relatives, should be provided the opportunity for informed decision making at an earlier age than average-risk men. (Albertsen, 2020) (Van Poppel et al, 2021). American Cancer Society guidelines for prostate cancer screening indicate that "Men who have at least a 10-y life expectancy should have an opportunity to make an informed decision with their health care provider about whether to be screened for prostate cancer after receiving information about the potential benefits, risks, and uncertainties associated with prostate cancer screening; prostate cancer screening should not occur without an informed decision-making process." (Smith et al, 2019). PSA is a glycoprotein produced almost exclusively in the epithelium of the prostate gland. In the circulation PSA may be complexed to serum proteins or may be free (fPSA) and together comprise total PSA (tPSA). The tPSA is normally less than 4 ng/mL (normal ranges vary depending upon which assay is used). A mildly increased tPSA in a patient with a very large prostate can be due to nodular hyperplasia, or to prostatitis, rather than carcinoma. The fPSA correlates more closely with benign prostatic conditions than the tPSA. A rising tPSA is suspicious for prostatic carcinoma. Transrectal needle biopsy, often guided by ultrasound, is useful to confirm the diagnosis, although incidental carcinomas can be found in transurethral resections for nodular hyperplasia. (Jung et al, 2006). Prostatic adenocarcinomas are composed of small glands that are back-to-back, with little or no intervening stroma. Cytologic features of adenocarcinoma include enlarged round, hyperchromatic nuclei that have a single prominent nucleolus. Mitotic figures suggest carcinoma. Less differentiated carcinomas have fused glands called cribriform glands, as well as solid nests or sheets of tumor cells, and many tumors have two or more of these patterns. Prostatic adenocarcinomas almost always arise in the posterior outer zone of the prostate and are often multifocal. (Pearson et al, 1996). Prostatic adenocarcinomas are usually graded according to the Gleason grading system based on the pattern of growth. There are 5 grades (from 1 to 5) based upon the architectural patterns. Adenocarcinomas of the prostate are given two grade based on the most common and second most common architectural patterns. These two grades are added to get a final grade of 2 to 10. The stage is determined by the size and location of the cancer, whether it has invaded the prostatic capsule or seminal vesicle, and whether it has metastasized. (Gleason, 1992) (Epstein, 2010). The grade and the stage correlate well with each other and with the prognosis. The prognosis of prostatic adenocarcinoma varies widely with tumor stage and grade. Cancers with a Gleason score of <6 are generally low grade and not aggressive. Advanced prostatic adenocarcinomas typically cause urinary obstruction, metastasize to regional (pelvic) lymph nodes and to the bones, causing blastic metastases in most cases. Metastases to the lungs and liver are seen in a minority of cases.


Many large nucleoi are seen here in the nuclei of cells in this prostatic adenocarcinoma.Adenocarcinoma of the prostate is common. It is the most common non-skin malignancy in elderly men. The prevalence of microscopic cancer may be 5% in men <30 years of age, and up to 59% by the age of 80 years . Many of these carcinomas remain small and clinically insignificant. However, some are not, and prostatic adenocarcinoma is second only to lung carcinoma as a cause for cancer-related deaths among men. (Bostwick et al, 2004) (Albertsen, 2020). Men with a higher likelihood of developing a prostate cancer (in the U.S.) include those of older age, black race, and family history. Those with an affected first-degree relative have a much greater risk. (Bostwick et al, 2004). Prostatic adenocarcinomas can be divided into two groups. The majority of these cancers are low-grade, indolent, and unlikely to cause death. Some prostate cancers are more aggressive, higher grade, and require treatment with systemic therapy for control. (Albertsen, 2020). Prostate cancers may be detected by digital examination, by magnetic resonance imaging, ultrasonography (transrectal ultrasound), or by screening with a blood test for prostate specific antigen (PSA). None of these methods can reliably detect all prostate cancers, particularly the small cancers. Widespread PSA screening is not cost-effective. Men whose life expectancy is less than 10 years may not pursue prostate cancer early detection because the likelihood of benefitis can be outweighed by the risk of harms from treatment. Men at higher risk for prostate cancer at earlier ages, including men of African ancestry or a family history of prostate cancer in nonelderly relatives, should be provided the opportunity for informed decision making at an earlier age than average-risk men. (Albertsen, 2020) (Van Poppel et al, 2021). American Cancer Society guidelines for prostate cancer screening indicate that "Men who have at least a 10-y life expectancy should have an opportunity to make an informed decision with their health care provider about whether to be screened for prostate cancer after receiving information about the potential benefits, risks, and uncertainties associated with prostate cancer screening; prostate cancer screening should not occur without an informed decision-making process." (Smith et al, 2019). PSA is a glycoprotein produced almost exclusively in the epithelium of the prostate gland. In the circulation PSA may be complexed to serum proteins or may be free (fPSA) and together comprise total PSA (tPSA). The tPSA is normally less than 4 ng/mL (normal ranges vary depending upon which assay is used). A mildly increased tPSA in a patient with a very large prostate can be due to nodular hyperplasia, or to prostatitis, rather than carcinoma. The fPSA correlates more closely with benign prostatic conditions than the tPSA. A rising tPSA is suspicious for prostatic carcinoma. Transrectal needle biopsy, often guided by ultrasound, is useful to confirm the diagnosis, although incidental carcinomas can be found in transurethral resections for nodular hyperplasia. (Jung et al, 2006). Prostatic adenocarcinomas are composed of small glands that are back-to-back, with little or no intervening stroma. Cytologic features of adenocarcinoma include enlarged round, hyperchromatic nuclei that have a single prominent nucleolus. Mitotic figures suggest carcinoma. Less differentiated carcinomas have fused glands called cribriform glands, as well as solid nests or sheets of tumor cells, and many tumors have two or more of these patterns. Prostatic adenocarcinomas almost always arise in the posterior outer zone of the prostate and are often multifocal. (Pearson et al, 1996). Prostatic adenocarcinomas are usually graded according to the Gleason grading system based on the pattern of growth. There are 5 grades (from 1 to 5) based upon the architectural patterns. Adenocarcinomas of the prostate are given two grade based on the most common and second most common architectural patterns. These two grades are added to get a final grade of 2 to 10. The stage is determined by the size and location of the cancer, whether it has invaded the prostatic capsule or seminal vesicle, and whether it has metastasized. (Gleason, 1992) (Epstein, 2010). The grade and the stage correlate well with each other and with the prognosis. The prognosis of prostatic adenocarcinoma varies widely with tumor stage and grade. Cancers with a Gleason score of <6 are generally low grade and not aggressive. Advanced prostatic adenocarcinomas typically cause urinary obstruction, metastasize to regional (pelvic) lymph nodes and to the bones, causing blastic metastases in most cases. Metastases to the lungs and liver are seen in a minority of cases.


A hallmark of prostatic adenocarcinoma is the presence of prominent large nucleoli, as seen here.Adenocarcinoma of the prostate is common. It is the most common non-skin malignancy in elderly men. The prevalence of microscopic cancer may be 5% in men <30 years of age, and up to 59% by the age of 80 years . Many of these carcinomas remain small and clinically insignificant. However, some are not, and prostatic adenocarcinoma is second only to lung carcinoma as a cause for cancer-related deaths among men. (Bostwick et al, 2004) (Albertsen, 2020). Men with a higher likelihood of developing a prostate cancer (in the U.S.) include those of older age, black race, and family history. Those with an affected first-degree relative have a much greater risk. (Bostwick et al, 2004). Prostatic adenocarcinomas can be divided into two groups. The majority of these cancers are low-grade, indolent, and unlikely to cause death. Some prostate cancers are more aggressive, higher grade, and require treatment with systemic therapy for control. (Albertsen, 2020). Prostate cancers may be detected by digital examination, by magnetic resonance imaging, ultrasonography (transrectal ultrasound), or by screening with a blood test for prostate specific antigen (PSA). None of these methods can reliably detect all prostate cancers, particularly the small cancers. Widespread PSA screening is not cost-effective. Men whose life expectancy is less than 10 years may not pursue prostate cancer early detection because the likelihood of benefitis can be outweighed by the risk of harms from treatment. Men at higher risk for prostate cancer at earlier ages, including men of African ancestry or a family history of prostate cancer in nonelderly relatives, should be provided the opportunity for informed decision making at an earlier age than average-risk men. (Albertsen, 2020) (Van Poppel et al, 2021). American Cancer Society guidelines for prostate cancer screening indicate that "Men who have at least a 10-y life expectancy should have an opportunity to make an informed decision with their health care provider about whether to be screened for prostate cancer after receiving information about the potential benefits, risks, and uncertainties associated with prostate cancer screening; prostate cancer screening should not occur without an informed decision-making process." (Smith et al, 2019). PSA is a glycoprotein produced almost exclusively in the epithelium of the prostate gland. In the circulation PSA may be complexed to serum proteins or may be free (fPSA) and together comprise total PSA (tPSA). The tPSA is normally less than 4 ng/mL (normal ranges vary depending upon which assay is used). A mildly increased tPSA in a patient with a very large prostate can be due to nodular hyperplasia, or to prostatitis, rather than carcinoma. The fPSA correlates more closely with benign prostatic conditions than the tPSA. A rising tPSA is suspicious for prostatic carcinoma. Transrectal needle biopsy, often guided by ultrasound, is useful to confirm the diagnosis, although incidental carcinomas can be found in transurethral resections for nodular hyperplasia. (Jung et al, 2006). Prostatic adenocarcinomas are composed of small glands that are back-to-back, with little or no intervening stroma. Cytologic features of adenocarcinoma include enlarged round, hyperchromatic nuclei that have a single prominent nucleolus. Mitotic figures suggest carcinoma. Less differentiated carcinomas have fused glands called cribriform glands, as well as solid nests or sheets of tumor cells, and many tumors have two or more of these patterns. Prostatic adenocarcinomas almost always arise in the posterior outer zone of the prostate and are often multifocal. (Pearson et al, 1996). Prostatic adenocarcinomas are usually graded according to the Gleason grading system based on the pattern of growth. There are 5 grades (from 1 to 5) based upon the architectural patterns. Adenocarcinomas of the prostate are given two grade based on the most common and second most common architectural patterns. These two grades are added to get a final grade of 2 to 10. The stage is determined by the size and location of the cancer, whether it has invaded the prostatic capsule or seminal vesicle, and whether it has metastasized. (Gleason, 1992) (Epstein, 2010). The grade and the stage correlate well with each other and with the prognosis. The prognosis of prostatic adenocarcinoma varies widely with tumor stage and grade. Cancers with a Gleason score of <6 are generally low grade and not aggressive. Advanced prostatic adenocarcinomas typically cause urinary obstruction, metastasize to regional (pelvic) lymph nodes and to the bones, causing blastic metastases in most cases. Metastases to the lungs and liver are seen in a minority of cases.


Chronic prostatitis is shown here.Acute prostatitis is not common, but is most likely to occur in young men. Causative agents include bacterial organisms similar to those causing urinary tract infections, as well as Neisseria gonorrheae. The related complication of prostatic abscess is uncommon. The edema and slight enlargement of the prostate with acute inflammation may cause acute rectal, lower back, or perineal pain along with fever. There can be dysuria. The prostate is enlarged and tender with palpation on digital rectal examination. Urine culture may be done, but prostatic massage is contraindicated. Microscopically, the glands are filled with neutrophils, explaining the presence of neutrophils on urine microscopic examination, and the intervening stroma may also contain a few neutrophils. Chronic prostatitis may follow acute prostatitis, but is more likely to occur without prior history in older men, and may suggest an underlying obstructive urinary tract abnormality. There can be intermittent urinary frequency and dysuria. The prostate may not be enlarged. Prostatic massage may increase the yield of urine culture. One common causative organism is difficult to grow in culture: Ureaplasma urealyticum. Chronic abacterial prostatitis is the most common cause for prostatitis, but is difficult to diagnose from lack of specific findings. No organism can be identified as a causative agent. Symptoms of dysuria along with low grade pelvic pain or low back pain may be present. Microscopically, lymphocytes, plasma cells, and macrophages appear in the prostatic stroma. Prostatitis can elevate the serum prostate specific antigen (PSA), but generally not more than double normal, and generally not increasing significantly over time. (Potts, 2001)


At low magnification, a needle biopsy of prostate is seen. The biopsy is filled with back-to-back glands with nuclei demonstrating hyperchromatism and pleomorphism. This is adenocarcinoma of prostate.Adenocarcinoma of the prostate is common. It is the most common non-skin malignancy in elderly men. The prevalence of microscopic cancer may be 5% in men <30 years of age, and up to 59% by the age of 80 years . Many of these carcinomas remain small and clinically insignificant. However, some are not, and prostatic adenocarcinoma is second only to lung carcinoma as a cause for cancer-related deaths among men. (Bostwick et al, 2004) (Albertsen, 2020). Men with a higher likelihood of developing a prostate cancer (in the U.S.) include those of older age, black race, and family history. Those with an affected first-degree relative have a much greater risk. (Bostwick et al, 2004). Prostatic adenocarcinomas can be divided into two groups. The majority of these cancers are low-grade, indolent, and unlikely to cause death. Some prostate cancers are more aggressive, higher grade, and require treatment with systemic therapy for control. (Albertsen, 2020). Prostate cancers may be detected by digital examination, by magnetic resonance imaging, ultrasonography (transrectal ultrasound), or by screening with a blood test for prostate specific antigen (PSA). None of these methods can reliably detect all prostate cancers, particularly the small cancers. Widespread PSA screening is not cost-effective. Men whose life expectancy is less than 10 years may not pursue prostate cancer early detection because the likelihood of benefitis can be outweighed by the risk of harms from treatment. Men at higher risk for prostate cancer at earlier ages, including men of African ancestry or a family history of prostate cancer in nonelderly relatives, should be provided the opportunity for informed decision making at an earlier age than average-risk men. (Albertsen, 2020) (Van Poppel et al, 2021). American Cancer Society guidelines for prostate cancer screening indicate that "Men who have at least a 10-y life expectancy should have an opportunity to make an informed decision with their health care provider about whether to be screened for prostate cancer after receiving information about the potential benefits, risks, and uncertainties associated with prostate cancer screening; prostate cancer screening should not occur without an informed decision-making process." (Smith et al, 2019). PSA is a glycoprotein produced almost exclusively in the epithelium of the prostate gland. In the circulation PSA may be complexed to serum proteins or may be free (fPSA) and together comprise total PSA (tPSA). The tPSA is normally less than 4 ng/mL (normal ranges vary depending upon which assay is used). A mildly increased tPSA in a patient with a very large prostate can be due to nodular hyperplasia, or to prostatitis, rather than carcinoma. The fPSA correlates more closely with benign prostatic conditions than the tPSA. A rising tPSA is suspicious for prostatic carcinoma. Transrectal needle biopsy, often guided by ultrasound, is useful to confirm the diagnosis, although incidental carcinomas can be found in transurethral resections for nodular hyperplasia. (Jung et al, 2006). Prostatic adenocarcinomas are composed of small glands that are back-to-back, with little or no intervening stroma. Cytologic features of adenocarcinoma include enlarged round, hyperchromatic nuclei that have a single prominent nucleolus. Mitotic figures suggest carcinoma. Less differentiated carcinomas have fused glands called cribriform glands, as well as solid nests or sheets of tumor cells, and many tumors have two or more of these patterns. Prostatic adenocarcinomas almost always arise in the posterior outer zone of the prostate and are often multifocal. (Pearson et al, 1996). Prostatic adenocarcinomas are usually graded according to the Gleason grading system based on the pattern of growth. There are 5 grades (from 1 to 5) based upon the architectural patterns. Adenocarcinomas of the prostate are given two grade based on the most common and second most common architectural patterns. These two grades are added to get a final grade of 2 to 10. The stage is determined by the size and location of the cancer, whether it has invaded the prostatic capsule or seminal vesicle, and whether it has metastasized. (Gleason, 1992) (Epstein, 2010). The grade and the stage correlate well with each other and with the prognosis. The prognosis of prostatic adenocarcinoma varies widely with tumor stage and grade. Cancers with a Gleason score of <6 are generally low grade and not aggressive. Advanced prostatic adenocarcinomas typically cause urinary obstruction, metastasize to regional (pelvic) lymph nodes and to the bones, causing blastic metastases in most cases. Metastases to the lungs and liver are seen in a minority of cases.


This is the gross appearance of nodular prostatic hyperplasia.Nodular prostatic hyperplasia (also termed benign prostatic hyperplasia, or BPH) is a common condition as men age. Perhaps a fourth of men have some degree of hyperplasia by the fifth decade of life. By the eighth decade, over 90% of males will have prostatic hyperplasia. However, in only a minority of cases (about 10%) will this hyperplasia be symptomatic and severe enough to require surgical or medical therapy. (Bushman, 2009). The mechanism for hyperplasia may be related to prostatic accumulation of dihydrotestosterone (DHT), formed from testosterone through the action of type 2 5α-reductase, an enzyme expressed mostly in stromal cells but not in prostatic epithelial cells. DHT binds to nuclear hormone receptors on both epithelial and stromal cells, stimulating growth. The effect of drugs which act to inhibit the enzyme 5-alpha reductase, which converts testosterone to dihydrotestosterone within cells. This blocks the growth-promoting androgenic effect and diminishes prostatic enlargement. Such drugs include finasteride and episteride. Drug therapy must be continued to remain effective. (Andríole et al, 2004). Another class of drugs used to treat BPH are the alpha 1-adrenoreceptors, including prazosin, alfuzosin, indoramin, terazosin, doxazosin, and tamsulosin. These alpha adrenergic blockers lead to relaxation of smooth muscle in prostate and help to relieve obstruction. Drug therapy must be continued to remain effective. (Auffenberg et al, 2009). The normal prostate weighs 20 to 30 gm, but most prostates with nodular hyperplasia can weigh from 50 to 100 gm. Hyperplasia begins in the region of the veru-montanum, in the inner zone of the prostate, and extends to involve lateral lobes. This enlargement impinges upon the prostatic urethra, leading to the difficulty on urination with hesitency that is typical for this condition. Dysuria, dribbling, and nocturia are also frequent. The urinary tract obstruction leads to urinary retention and risk for infection. In severe, prolonged cases, hydroureter with hydronephrosis and renal failure can ensue. (Wasserman, 2006). Microscopically, nodular prostatic hyperplasia consists of proliferating nodules of glands and intervening stroma. Most of the hyperplasia is contributed by glandular epithelial cell proliferation, but the stroma is also increased, and in rare cases may predominate. The glands may be more variably sized, with larger glands having more prominent papillary infoldings. Nodular hyperplasia is NOT a precursor to carcinoma. (Homma et al, 1996)


This is the microscopic appearance of nodular prostatic hyperplasia at low magnification. Note the nodule filled with enlarged glands. Though crowded, there is still stroma between the glands.Nodular prostatic hyperplasia (also termed benign prostatic hyperplasia, or BPH) is a common condition as men age. Perhaps a fourth of men have some degree of hyperplasia by the fifth decade of life. By the eighth decade, over 90% of males will have prostatic hyperplasia. However, in only a minority of cases (about 10%) will this hyperplasia be symptomatic and severe enough to require surgical or medical therapy. (Bushman, 2009). The mechanism for hyperplasia may be related to prostatic accumulation of dihydrotestosterone (DHT), formed from testosterone through the action of type 2 5α-reductase, an enzyme expressed mostly in stromal cells but not in prostatic epithelial cells. DHT binds to nuclear hormone receptors on both epithelial and stromal cells, stimulating growth. The effect of drugs which act to inhibit the enzyme 5-alpha reductase, which converts testosterone to dihydrotestosterone within cells. This blocks the growth-promoting androgenic effect and diminishes prostatic enlargement. Such drugs include finasteride and episteride. Drug therapy must be continued to remain effective. (Andríole et al, 2004). Another class of drugs used to treat BPH are the alpha 1-adrenoreceptors, including prazosin, alfuzosin, indoramin, terazosin, doxazosin, and tamsulosin. These alpha adrenergic blockers lead to relaxation of smooth muscle in prostate and help to relieve obstruction. Drug therapy must be continued to remain effective. (Auffenberg et al, 2009). The normal prostate weighs 20 to 30 gm, but most prostates with nodular hyperplasia can weigh from 50 to 100 gm. Hyperplasia begins in the region of the veru-montanum, in the inner zone of the prostate, and extends to involve lateral lobes. This enlargement impinges upon the prostatic urethra, leading to the difficulty on urination with hesitency that is typical for this condition. Dysuria, dribbling, and nocturia are also frequent. The urinary tract obstruction leads to urinary retention and risk for infection. In severe, prolonged cases, hydroureter with hydronephrosis and renal failure can ensue. (Wasserman, 2006). Microscopically, nodular prostatic hyperplasia consists of proliferating nodules of glands and intervening stroma. Most of the hyperplasia is contributed by glandular epithelial cell proliferation, but the stroma is also increased, and in rare cases may predominate. The glands may be more variably sized, with larger glands having more prominent papillary infoldings. Nodular hyperplasia is NOT a precursor to carcinoma. (Homma et al, 1996)


This is the microscopic appearance of nodular prostatic hyperplasia at medium power. Note that the columnar arrangement of cells near the gland lumina is preserved. Note several pink corpora amylacea in gland lumens.Nodular prostatic hyperplasia (also termed benign prostatic hyperplasia, or BPH) is a common condition as men age. Perhaps a fourth of men have some degree of hyperplasia by the fifth decade of life. By the eighth decade, over 90% of males will have prostatic hyperplasia. However, in only a minority of cases (about 10%) will this hyperplasia be symptomatic and severe enough to require surgical or medical therapy. (Bushman, 2009). The mechanism for hyperplasia may be related to prostatic accumulation of dihydrotestosterone (DHT), formed from testosterone through the action of type 2 5α-reductase, an enzyme expressed mostly in stromal cells but not in prostatic epithelial cells. DHT binds to nuclear hormone receptors on both epithelial and stromal cells, stimulating growth. The effect of drugs which act to inhibit the enzyme 5-alpha reductase, which converts testosterone to dihydrotestosterone within cells. This blocks the growth-promoting androgenic effect and diminishes prostatic enlargement. Such drugs include finasteride and episteride. Drug therapy must be continued to remain effective. (Andríole et al, 2004). Another class of drugs used to treat BPH are the alpha 1-adrenoreceptors, including prazosin, alfuzosin, indoramin, terazosin, doxazosin, and tamsulosin. These alpha adrenergic blockers lead to relaxation of smooth muscle in prostate and help to relieve obstruction. Drug therapy must be continued to remain effective. (Auffenberg et al, 2009). The normal prostate weighs 20 to 30 gm, but most prostates with nodular hyperplasia can weigh from 50 to 100 gm. Hyperplasia begins in the region of the veru-montanum, in the inner zone of the prostate, and extends to involve lateral lobes. This enlargement impinges upon the prostatic urethra, leading to the difficulty on urination with hesitency that is typical for this condition. Dysuria, dribbling, and nocturia are also frequent. The urinary tract obstruction leads to urinary retention and risk for infection. In severe, prolonged cases, hydroureter with hydronephrosis and renal failure can ensue. (Wasserman, 2006). Microscopically, nodular prostatic hyperplasia consists of proliferating nodules of glands and intervening stroma. Most of the hyperplasia is contributed by glandular epithelial cell proliferation, but the stroma is also increased, and in rare cases may predominate. The glands may be more variably sized, with larger glands having more prominent papillary infoldings. Nodular hyperplasia is NOT a precursor to carcinoma. (Homma et al, 1996)


This is prostatic intraepithelial neoplasia (PIN), a precancerous cellular proliferation found in a single acinus or small group of acini. PIN can be low or high grade (as seen here). The finding of PIN suggests that prostatic adenocarcinoma may also be present (about half the time with high grade PIN).Prostatic intraepithelial neoplasia (PIN), which is dysplasia of the epithelium lining prostate glands, is a probable precursor of prostatic carcinoma. The appearance of PIN may precede carcinoma by 10 or more years. It can be divided into low grade and high grade PIN. Low grade PIN may be found even in men in middle age. PIN does not routinely increase the serum prostate specific antigen (PSA). PIN usually involves an acinus or a small cluster of acini, but it can be more extensive on occasion. The acini are usually medium-sized to large, with rounded borders. The partial involvement of an acinus is a helpful feature to distinguish PIN from adenocarcinoma. PIN is characterized histologically by progressive basal cell alyer disruption, loss of markers of secretory differentiation, nuclear and nucleolar abnormalities, increasing proliferative potential, increasing microvessel density, variation in DNA content, and allelic loss. Unlike adenocarcinoma, with which it may coexist, glands with PIN retain an intact or fragmented basal cell layer. (Ayala and Ro, 2007). Low grade PIN has epithelial cells that are crowded and irregularly spaced, with nuclei that are hyperchromatic and pleomorphic, with small nucleoli. High grade PIN has even more hyperchromatism and pleomorphism, the cells are more crowded and heaped up, and nucleoli can be prominent. Immunohistochemical staining with antibody to low molecular weight keratin can help to identify the fragmented basal cell layer. Anti-androgenic drug therapy may cause regression of PIN. (Ayala and Ro, 2007). The appearance of PIN warrants increased surveillance of the prostate for development of an invasive carcinoma because the presence of PIN that is high grade suggests an increased risk for subsequent appearance of adenocarcinoma. PIN itself is not an indication for aggressive treatment. (Lipski et al, 1996)


Compare the normal prostatic gland at the left with the group of acini at the right with prostatic intraepithelial neoplasia (PIN), a precancerous cellular proliferation found in a single acinus or small group of acini.Prostatic intraepithelial neoplasia (PIN), which is dysplasia of the epithelium lining prostate glands, is a probable precursor of prostatic carcinoma. The appearance of PIN may precede carcinoma by 10 or more years. It can be divided into low grade and high grade PIN. Low grade PIN may be found even in men in middle age. PIN does not routinely increase the serum prostate specific antigen (PSA). PIN usually involves an acinus or a small cluster of acini, but it can be more extensive on occasion. The acini are usually medium-sized to large, with rounded borders. The partial involvement of an acinus is a helpful feature to distinguish PIN from adenocarcinoma. PIN is characterized histologically by progressive basal cell alyer disruption, loss of markers of secretory differentiation, nuclear and nucleolar abnormalities, increasing proliferative potential, increasing microvessel density, variation in DNA content, and allelic loss. Unlike adenocarcinoma, with which it may coexist, glands with PIN retain an intact or fragmented basal cell layer. (Ayala and Ro, 2007). Low grade PIN has epithelial cells that are crowded and irregularly spaced, with nuclei that are hyperchromatic and pleomorphic, with small nucleoli. High grade PIN has even more hyperchromatism and pleomorphism, the cells are more crowded and heaped up, and nucleoli can be prominent. Immunohistochemical staining with antibody to low molecular weight keratin can help to identify the fragmented basal cell layer. Anti-androgenic drug therapy may cause regression of PIN. (Ayala and Ro, 2007). The appearance of PIN warrants increased surveillance of the prostate for development of an invasive carcinoma because the presence of PIN that is high grade suggests an increased risk for subsequent appearance of adenocarcinoma. PIN itself is not an indication for aggressive treatment. (Lipski et al, 1996)