Novel male contraceptive options are predicted to reduce the incidence unintended pregnancies, [ 25 ] [ 18 ]  and being the product of an intended rather than unintended pregnancy has been shown to correlate with improved health and wellbeing outcomes in children. [ 31 ] [ 222 ] [ 233 ] [ 234 ]   Additionally, reduced family size correlates with improved educational outcomes, [ 235 ]  and children born after the introduction of family planning programs in the USA experienced a reduction in poverty rates, both in childhood and adulthood. [ 236 ]


Unintended pregnancies rates increase as income decreases, both between countries [ 36 ]  and between socioeconomic and racial groups within a given country. [ 211 ] [ 237 ]   Women of color, especially Black women, in the United States and other developed countries have dramatically higher rates of  death during and after birth  and worse maternal health outcomes, due in part to  systemic discrimination . [ 238 ] [ 222 ]   Since unintended pregnancies can have negative effects on an individual's physical and mental health, educational attainment, and economic prospects, these higher unintended pregnancy rates likely contribute to the persistent socioeconomic gaps within and between societies. [ 27 ] [ 29 ] [ 30 ] [ 31 ] [ 32 ] [ 33 ] [ 34 ]     It’s therefore possible that the introduction of new male contraceptives would not only mitigate gender inequities, as discussed above, but racial and income inequities as well, by providing more ways for individuals to avoid unintended pregnancies. [ 25 ]


In addition to the personal financial savings of avoiding unintended pregnancy mentioned above, on a societal level, contraceptives are a public health intervention with a high return on investment: for every dollar the United States government spends on family planning programs, it saves $7.09, for a total of over $13 billion per year. [ 239 ]   Unintended pregnancies in the United States are estimated to cause $4.5 billion in direct medical costs. [ 34 ] [ 32 ]   New male contraceptives are likely to prevent some unintended pregnancies [ 25 ]  and therefore reduce these costs.


61% of unintended pregnancies end in  abortion , [ 35 ]  whereas only 20% of all pregnancies end in abortion. [ 240 ]  Interestingly, unintended pregnancy rates are higher in countries where abortion is illegal than those where abortion is legal, yet the incidence of abortion is similar between these groups of countries. [ 35 ] [ 241 ]   Illegal abortions are more likely to be  unsafe , and there are an estimated 25 million unsafe abortions globally each year, leading to 50,000 - 70,000 yearly deaths and 5 million people with long-term health consequences. [ 37 ] [ 38 ] [ 39 ] [ 40 ]    Importantly, increases in the prevalence and uptake of modern contraceptives have been shown to decrease unintended pregnancy and abortion rates when fertility rates are constant. [ 242 ] [ 243 ] [ 244 ]   This suggests that the introduction of new forms of male contraception could prevent a significant number of abortions, save lives, and avoid unnecessary suffering.


A variety of plant extracts have been used throughout history in attempts to prevent pregnancy, though most were used by women, and the efficacy and safety of these methods is questionable. [ 245 ] [ 246 ] [ 247 ]


Condoms  made of animal organs or fabric have been in documented use since at least the 16th century, [ 248 ]  and various types of penile coverings have been depicted and referenced in materials from cultures around the world as early as 3000  BCE , though it is not always clear that these coverings were used for birth control or protection from sexually transmitted infections. [ 249 ]   The 1800's saw the development of thick reusable rubber condoms, [ 248 ] [ 249 ]  and thinner disposable latex rubber condoms entered production in the 1920s. [ 250 ] [ 251 ] [ 252 ]


Vasectomy  was first performed in humans in the late 1800s, but not initially as a method of voluntary birth control.  Instead, it was first used as an attempted treatment (later proved to be ineffective) for  enlarged prostates , and within a few years, one-sided vasectomy became popular as a supposed method of sexual rejuvenation in older men. [ 253 ] [ 254 ]   Although this rejuvenation treatment was ineffective  pseudoscience  and any perceived effects were likely due only to the  placebo effect , many prominent men, such as Sigmund Freud and W.B. Yeats, sought out the procedure. [ 255 ]   In the early 1900s, the use of vasectomy took a darker turn, and it became widely promoted and practiced as a means of  eugenic  involuntary sterilization. [ 254 ] [ 253 ]   It was not until the 1950s that vasectomy became widely used as a method for voluntary sterilization and family planning. [ 254 ] [ 253 ]   Since then, vasectomy has undergone extensive technical improvements and innovations, such that it is no longer a single procedure, but a  family of related procedures . [ 253 ] [ 256 ]


In the 1990s, and into the early 2000s, major pharmaceutical companies  Organon ,  Wyeth , and  Schering  were pursuing preclinical and clinical development of various male contraceptive products, but in 2006, all three companies ceased development of these products within a short time of each other, for reasons that have not been publicly released. [ 257 ] [ 110 ]


In 2013, the Male Contraceptive Initiative was founded with the goal of funding and supporting the development of new male contraceptives. [ 258 ] [ 259 ]


In 2020,  Dr. Polina Lishko  was awarded the  MacArthur "Genius" Fellowship  for her contributions to the understanding of sperm physiology, with the award specifically noting her work on "opening up new avenues in ... the development of male-specific or unisex contraceptives." [ 260 ]


Many researchers have attempted to develop male contraceptive products over the last hundred years.  A selection of these efforts (that are no longer in development as of 2024) are listed below.


In  urology , the  Mitrofanoff principle  is the creation of a passageway for  urine  or  enema  fluid that, by its ( surgical ) construction, has a  valve  mechanism to allow  continence . [ 1 ]


Procedures which make use of the Mitrofanoff principle:


It is named after the  French   urologist  (Mitrofanoff) who popularized it. [ 2 ]


Nocturnal enuresis  ( NE ), also informally called  bedwetting , is  involuntary urination  while  asleep  after the age at which  bladder  control usually begins. [ 1 ]  Bedwetting in children and adults can result in emotional stress. [ 2 ]  Complications can include  urinary tract infections . [ 2 ] [ 3 ] [ 4 ] [ 5 ]


Most bedwetting is a  developmental delay —not an emotional problem or physical illness. Only a small percentage (5 to 10%) of bedwetting cases have a specific medical cause. [ 6 ]  Bedwetting is commonly associated with a  family history  of the condition. [ 7 ]  Nocturnal  enuresis  is considered  primary  when a child has not yet had a prolonged period of being dry.  Secondary  nocturnal enuresis is when a child or adult begins wetting again after having stayed dry.


Treatments range from  behavioral therapy , such as  bedwetting alarms , to medication, [ 8 ] [ 9 ]  such as  hormone replacement , and even surgery such as  urethral dilatation . Since most bedwetting is simply a developmental delay, most treatment plans aim to protect or improve  self-esteem . [ 6 ]  Treatment guidelines recommend that the physician counsel the parents, [ 10 ]  warning about psychological consequences caused by pressure, shaming, or punishment for a condition children cannot control. [ 6 ]


Bedwetting is the most common childhood complaint. [ 11 ] [ 12 ] [ 13 ]


A review of medical literature shows doctors consistently stressing that a bedwetting child is not at fault for the situation. Many medical studies state that the psychological impacts of bedwetting are more important than the physical considerations. "It is often the child's and family members' reaction to bedwetting that determines whether it is a problem or not." [ 14 ]


Whether bedwetting causes low self-esteem remains a subject of debate, but several studies have found that self-esteem improved with management of the condition. [ 15 ]


Children questioned in one study ranked bedwetting as the third most stressful life event, after "parental war of words", divorce and parental fighting. Adolescents in the same study ranked bedwetting as tied for second with parental fighting. [ 15 ]


Bedwetters face problems ranging from being teased by siblings, being punished by parents, the embarrassment of still having to wear diapers, and being afraid that friends will find out.


Psychologists report that the amount of psychological harm depends on whether the bedwetting harms self-esteem or development of social skills. Key factors are: [ 16 ] [ unreliable medical source? ]


Studies indicate that children with behavioral problems are more likely to wet their beds. For children who have developmental problems, the behavioral problems and the bedwetting are frequently part of/caused by the developmental issues. For bedwetting children without other developmental issues, these behavioral issues can result from self-esteem issues and stress caused by the wetting. [ 16 ] [ unreliable medical source? ]


As mentioned below, current studies show that it is very rare for a child to intentionally wet the bed as a method of acting out. [ citation needed ]


Medical literature states, and studies show, that punishing or shaming a child for bedwetting will frequently make the situation worse. It is best described as a downward cycle, where a child punished for bedwetting feels shame and a loss of self-confidence. This can cause increased bedwetting incidents, leading to more punishment and shaming. [ 17 ]


In the United States, about 25% of enuretic children are punished for wetting the bed. [ 18 ]  In Hong Kong, 57% of enuretic children are punished for wetting. [ 19 ]  Parents with only a grade-school level education punish bedwetting children at twice the rate of high-school- and college-educated parents. [ 18 ]


In  Korea  and in small parts of  Japan , there is a folk tradition whereby bedwetters are made to wear a  winnowing basket  on their head and sent to ask their neighbors for salt. This is motivated in part by a desire to publicly embarrass the child into compliance, as neighbors would recognize why the child was knocking on their door. [ 20 ]


Parents and family members are frequently stressed by a child's bedwetting. Soiled linens and clothing cause additional laundry. Wetting episodes can cause lost sleep if the child wakes and/or cries, waking the parents. A European study estimated that a family with a child who wets nightly will pay about $1,000 a year for additional laundry, extra sheets, diapers, and mattress replacement. [ 15 ]


Despite these stressful effects, doctors emphasize that parents should react patiently and supportively. [ 21 ]


Bedwetting does  not  indicate a greater possibility of being a  sociopath , as long as caregivers do not cause trauma by shaming or punishing a bedwetting child. Bedwetting was part of the  Macdonald triad , a set of three behavioral characteristics described by  John Macdonald  in 1963. [ 22 ]  The other two characteristics were  firestarting  and  animal abuse . Macdonald suggested that there was an association between a person displaying all three characteristics, then later displaying  sociopathic  criminal behavior. [ 23 ]


Up to 60% of multiple murderers, according to some estimates, wet their beds post-adolescence. [ 24 ]


Enuresis is an "unconscious, involuntary [...] act". [ 25 ]


Bedwetting can be connected to past emotions and identity. Children under substantial stress, particularly in their home environment, frequently engage in bedwetting, in order to alleviate the stress produced by their surroundings. [ citation needed ]  Trauma can also trigger a return to bedwetting (secondary enuresis) in both children and adults.


It is not bedwetting that increases the chance of criminal behavior, but the associated trauma. [ 26 ]  Parental cruelty can result in "homicidal proneness". [ 27 ]


The  etiology  of NE is not fully understood, although there are three common causes: excessive urine volume, poor sleep arousal, and bladder contractions. Differentiation of cause is mainly based on patient history and fluid charts completed by the parent or carer to inform management options. [ 28 ] [ 29 ]


Bedwetting has a strong genetic component. Children whose parents were not enuretic have only a 15% incidence of bedwetting. When one or both parents were bedwetters, the rates jump to 44% and 77% respectively. [ 30 ]


These first two factors (aetiology and genetic component) are the most common in bedwetting, but current medical technology offers no easy testing for either cause. There is no test to prove that bedwetting is only a developmental delay, and  genetic testing  offers little or no benefit. As a result, other conditions should be ruled out. The following causes are less common, but are easier to prove and more clearly treated: [ citation needed ]


In some bedwetting children there is no increase in ADH (antidiuretic hormone) production, while other children may produce an increased amount of ADH but their response is insufficient. [ 28 ] [ 31 ]


Two physical functions prevent bedwetting. The first is a  hormone  that reduces  urine  production at night. The second is the ability to wake up when the  bladder  is full. Children usually achieve nighttime dryness by developing one or both of these abilities. There appear to be some  hereditary  factors in how and when these develop. [ 49 ]


The first ability is a  hormone  cycle that reduces the body's urine production. At about sunset each day, the body releases a minute burst of  antidiuretic hormone  (also known as arginine vasopressin or AVP). This hormone burst reduces the  kidney 's urine output well into the night so that the bladder does not get full until morning. This hormone cycle is not present at birth. Many children develop it between the ages of two and six years old, others between six and the end of  puberty , and some not at all. [ 50 ]


The second ability that helps people stay dry is waking when the bladder is full. This ability develops in the same age range as the vasopressin hormone, but is separate from that hormone cycle.


The typical development process begins with one- and two-year-old children developing larger bladders and beginning to sense bladder fullness. Two- and three-year-old children begin to stay dry during the day. Four- and five-year-olds develop an adult pattern of urinary control and begin to stay dry at night. [ 6 ]


Thorough history regarding frequency of bedwetting, any period of dryness in between, associated daytime symptoms, constipation, and encopresis should be sought.


Nocturnal urinary continence is dependent on three factors: 1) nocturnal urine production, 2) nocturnal bladder function and 3) sleep and arousal mechanisms. Any child will experience nocturnal enuresis if more urine is produced than can be contained in the bladder or if the detrusor is hyperactive, provided that he or she is not awakened by the imminent bladder contraction. [ 53 ]


Primary nocturnal enuresis is the most common form of bedwetting. Bedwetting becomes a disorder when it persists after the age at which bladder control usually occurs (4–7 years), and is either resulting in an average of at least two wet nights a week with no long periods of dryness or not able to sleep dry without being taken to the toilet by another person.


New studies show that anti-psychotic drugs can have a side effect of causing enuresis. [ 54 ]


It has been shown that diet impacts enuresis in children.  Constipation  from a poor diet can result in impacted stool in the colon putting undue pressure on the bladder creating loss of bladder control ( overflow incontinence ). [ 55 ]


Some researchers, however, recommend a different starting age range. This guidance says that bedwetting can be considered a clinical problem if the child regularly wets the bed after turning 7 years old. [ 14 ]


Secondary enuresis occurs  after  a patient goes through an extended period of dryness at night (six months or more) and then  reverts  to night-time wetting. Secondary enuresis can be caused by emotional stress or a medical condition, such as a bladder infection. [ 56 ]


Psychologists are usually allowed to diagnose and write a prescription for diapers if nocturnal enuresis causes the patient significant distress. [ 57 ]  Psychiatists may instead use a definition from the  DSM-IV , defining nocturnal enuresis as repeated urination into bed or clothes, occurring twice per week or more for at least three consecutive months in a child of at least 5 years of age and not due to either a  drug side effect  or a  medical condition .


There are a number of management options for bedwetting. The following options apply when the bedwetting is not caused by a specifically identifiable medical condition such as a bladder abnormality or diabetes. Treatment is recommended when there is a specific medical condition such as  bladder  abnormalities,  infection , or  diabetes . It is also considered when bedwetting may harm the child's  self-esteem  or relationships with family/friends. Only a small percentage of bedwetting is caused by a specific medical condition, so most treatment is prompted by concern for the child's  emotional  welfare. Behavioral treatment of bedwetting overall tends to show increased self-esteem for children. [ 58 ] [ 59 ]


Parents become concerned much earlier than doctors. A study in 1980 asked parents and physicians the age that children should stay dry at night. The average parent response was 2.75 years old, while the average physician response was 5.13 years old. [ 60 ]


Punishment is not effective and can interfere with treatment.


Simple behavioral methods are recommended as initial treatment. [ 61 ]  Other treatment methods include the following:


Doctors frequently consider bedwetting as a self-limiting problem, since most children will outgrow it. Children 5 to 9 years old have a spontaneous cure rate of 14% per year. Adolescents 10 to 17 years old have a spontaneous cure rate of 16% per year. [ 78 ]


As can be seen from the numbers above, a portion of bedwetting children will not outgrow the problem. Adult rates of bedwetting show little change due to spontaneous cure. Persons who are still enuretic at age 17 are likely to deal with bedwetting throughout their lives. [ 78 ]


Studies of bedwetting in adults have found varying rates. The most quoted study in this area was done in the Netherlands. It found a 0.5% rate for 20- to 79-year-olds. A Hong Kong study, however, found a much higher rate. The Hong Kong researchers found a bedwetting rate of 2.3% in 16- to 40-year-olds. [ 78 ]


In the first century B.C., at lines 1026-29 of the fourth book of his  On the Nature of Things ,  Lucretius  gave a high-style description of bed-wetting: [ 79 ]


An early psychological perspective on bedwetting was given in 1025 by  Avicenna  in  The Canon of Medicine : [ 81 ]


Psychological theory through the 1960s placed much greater focus on the possibility that a bedwetting child might be acting out, purposefully striking back against parents by soiling linens and bedding. However, more recent research and medical literature states that this is very rare. [ 82 ] [ 83 ]


PC3  ( PC-3 ) is a human  prostate cancer   cell line  used in prostate cancer research and drug development. [ 1 ]  PC3 cells are useful in investigating biochemical changes in advanced prostate cancer cells and in assessing their response to  chemotherapeutic agents . PC3 cells are also used to study viral infection in mammalian cells that exhibit an immune response. [ 2 ]


The PC3 cell line was established in 1979 from bone metastasis of grade IV of  prostate  cancer in a 62-year-old Caucasian male. [ 3 ]  These cells do not respond to androgens, glucocorticoids or fibroblast growth factors, [ 4 ]  but results suggest that the cells are influenced by epidermal growth factors. [ 5 ]  PC3 cells can be used to create subcutaneous tumor  xenografts  in mice to investigate the tumor environment and therapeutic drug functionality. [ 6 ]


PC3 cells have high  metastatic  potential compared to other pancreatic cells of  DU145  cells, which have a moderate metastatic potential, and to  LNCaP  cells, which have low metastatic potential. [ citation needed ]  Comparisons of the  protein expression  of PC3, LNCaP, and other cells have shown that PC3 is characteristic of small cell neuroendocrine carcinoma. [ 4 ]


PC3 cells have low  testosterone - 5-alpha reductase  and  acidic phosphatase  activity, and do not express PSA ( prostate-specific antigen ). Furthermore,  karyotypic  analysis has shown that PC3 are near-triploid, having 62 chromosomes. Q-band analysis showed no Y chromosome. From a morphological point of view,  electron microscopy  revealed that PC3 cells show characteristics of a poorly-differentiated  adenocarcinoma . They have features common to neoplastic cells of epithelial origins, such as numerous microvilli, junctional complexes, abnormal nuclei and nucleoli, abnormal mitochondria, annulate lamellae, and lipoidal bodies. [ citation needed ]


There are a variety of Different PC3 cell lines derived from the original PC3 cell line. The most common include PC3-PR Cells, PC-3M Cells, PC3-EGFP Cells, PC3-Dox Cells, PC3-LacZ Cells, PC3-AR Cells. Each of these have different morphological and physiological properties but they all originate from the original PC3 cell derived from the 62-year old caucasian male. [ 3 ]


C3-PR cells are Paclitaxel-Resistant cells that, unlike PC3 cells, are resistant with  Paclitaxel  (PTX). In these cells PTX is unable to stimulate p21 and acetylated α-tubulin expression of PC3-PR cells. Though  Cabazitaxel  and  HDAC  inhibitors were able to induce p21 and α-tubulin, these equally suppress PC3-PR cells. Due to the suppression ability of Cabazitaxel and HDAC, these drugs are able to replace the common chemotherapy drug in PC3-PR cells. [ 7 ]  These cells allow researchers to develop strategies in order to treat prostate cancer that is resistant to traditional chemotherapy drugs.


PC-3M Cells (Metastatic)


PC-3-M cells are a highly metastatic form of PC3 cells. They metastasize in a much more prolific fashion than regular PC3 cells. These cells are used in research to study the potential treatments of PC’s that are highly metastatic. PC3-M is used in research from in-vitro to in-vivo model animals for cancer research. [ 8 ]  This cell line is able to research the most dangerous, advanced forms of pancreatic cancer, as the high metastasis potential will allow these cells to spread throughout the body in a rapid fashion.


PC3-EGFP Cells (Enhanced Green Fluorescent Protein)


PC3-EGFP are PC3 cells that have been modified in order to express green fluorescent proteins at a higher rate. This is visible when EGFP expression levels are analyzed. [ 9 ]  This allows for live tracking of PC3 cells as well as real time imaging. This can be especially useful when studying the proliferation as well as the drug response in PC3 cells.


PC3-Dox Cells


PC3-Dox cells are modified to be resistant to Doxorubicin. This cell line is used to study multidrug resistance (MDR) in PC3. Specifically miR-21 research is based on this lineage of cells in order to determine if it is possible to reverse (MDR) through the employment of this drug. Additionally these cells look at if it is possible to resensitize PC3 cells to Doxorubicin. [ 10 ]


PC3-Ras Cells
PC3-Ras cells are modified in order to express the oncogene ras. Ras is involved in the activation of downstream effectors that play a role in DNA transcription. This modification allows researchers to study the role of Ras signaling in prostate cancer. This is very important to studying the processes of tumor progression, metastasis, and drug resistance in pancreatic cancer cells, as it is tied to mitosis. [ 11 ]


Prostate cancer (PC) is the most common form of non-cutaneous malignant cancer in males, and is the second leading cause of cancer deaths in males. [ 12 ]  PC3 cells have been utilized to research aggressive and castration-resistant forms of pancreatic cancer. The androgen-independence of these cells during cell division makes them invaluable for studying the molecular mechanisms embedded in studying advanced prostate cancer.  [ 13 ]  PC3 cells have been involved in research regarding the prevention and treatment of prostate cancer. PC3 cells have been used in research surrounding Methylene Blue Photodynamic Laser Therapy (MB-PDT) and  Sulforaphane (SFN) . Research published in 2023 utilizing PC3 cells illustrated that MB-PDT treatment decreased the antioxidant potential and increased lipid peroxidation, decreasing the viability and metastatic capacity of PC3 cells. The results from this study further support other research that MB-PDT can be used in conjunction with traditional therapies to treat aggressive versions of prostate cancers. [ 14 ]  SFN treatments have been used to treat prostate cancer as well as many other tumors. SFN is a plant-derived chemical present in many plants, especially broccoli and broccoli sprouts; though there are concerns about the bioavailability of SFN supplements.  [ 15 ]  Nevertheless, many prostate cancer patients have turned to SFN to prevent growth of PCs resistant to many of the traditional forms of treatment. Experimentation in 2020 linked SFN to a decrease in prostate cancer proliferation and growth, using PC3 cells alongside  DU145 . These studies found that using treatments as low as 1 µM of SFN decreased PC3 cell count by 50% in-vitro.  [ 16 ]


This  cell biology  article is a  stub . You can help Wikipedia by  expanding it .


Pediatric urology  is a surgical subspecialty of medicine dealing with the disorders of children's genitourinary systems. Pediatric urologists provide care for both boys and girls ranging from birth to early adult age. The most common problems are those involving disorders of urination, reproductive organs and testes.


Some of the problems they deal with are: [ citation needed ]


In North America, most pediatric urologists are associated with  children's hospitals . Training for  board certification  in pediatric urology typically consists of a surgery internship as part of a urology  residency  followed by subspecialty training in pediatric urology at a major children's hospital. In India, Pediatric Urology is practiced by Pediatric Surgeons with a special interest/ training in pediatric urology as well as by adult urologists who get trained in Pediatric Urology. [ citation needed ]


Pelvic compression syndrome  is characterized by intermittent or persisting pain in the  abdomen , which is  exacerbated  by abdominal pressure. A swelling of the  veins  in the valveless  pampiniform plexus  causes it.


While  varicocele  is the diagnostic term for swelling in the valveless venous distribution of the male  pampiniform plexus , this  embryological  structure, common to males and females, is often incidentally noted to be swollen during  laparoscopic  examinations in both  symptomatic  and  asymptomatic  females. [ 1 ]  Diagnosis of female varicocele, properly called pelvic compression syndrome, should be expected to be as frequent as male varicocele (15% of healthy asymptomatic men, which are thought to develop primarily during puberty and prevalence increases approximately 10% per decade of life  [ 2 ] ).


While one may expect the female to have an equal  prevalence  of pelvic compression syndrome due to the identical  embryological  origin of the valveless  pampiniform plexus , this condition is thought to be underdiagnosed due to the broad differential of the pain pattern:  unilateral or bilateral  pain, dull to sharp, constant to intermittent pain worsening with any increase in  abdominal pressure . [ 3 ]


Physical exam has a specificity of 77% and sensitivity of nearly 94% when the patient is noted to be tender over  adnexa  during physical examination with a history of postcoital pain for differentiating  pelvic congestion syndrome  from other  pathologies  of pelvic origin. [ 4 ]


Confirmatory imaging requires  ultrasound  while performing a  Valsalva maneuver , while the gold standard remains  ovarian  and iliac  catheter   venography  showing veins 5-10mm in diameter during the Valsalva maneuver.


Complete resolution of symptoms after  menopause  indicates the influence of hormones on  pelvic congestion syndrome .  Estrogen  is a venous dilator and can thus produce the venous dilation implicated in the  pathophysiology  of the PCS. [ 3 ]


Penis  clamp  is an external penis compression  device  that treats male  urinary incontinence . Incontinence clamps for men are applied to compress the  urethra  to compensate for the malfunctioning of the natural  urinary sphincter , preventing leakage from the  bladder  with minimal restriction of blood flow.


These devices are crafted to block or compress the urethra, thus preventing urine leakage. They are applied externally and are typically user-friendly and comfortable to use. Compression devices may vary in shape and size, but they are generally made of flexible and soft materials that adapt to the anatomical contour. Some models come with adjustable settings to customize the level of compression according to individual needs. There were models of urethra clamping devices that date back from the 1920s. They are most commonly made from stainless steel and plastic on the outer surface and  silicone  or  rubber  on the inner surface. They are usually applied as a cost-effective solution to urinary incontinence. [ 1 ]


Cunningham Penile Clamp: This type of clamp is placed around the penis. It helps to stop urine leakage by compressing the urethra, the tube through which urine exits. This is achieved by controlled squeezing, preventing urine from escaping.


Flexible Uriclak Device: Another type of clamp that is also placed on the penis. It functions similarly to the Cunningham penile clamp by compressing the urethra, but in this case, it does not have closures. It is flexible and comfortably adapts to halt urine flow.


Non-invasive: These devices do not require surgery or invasive procedures, making them an attractive option for individuals looking to avoid surgical interventions.


Customization: Penile clamps allow for personalized adjustments to cater to individual needs and preferences.


Independence and Freedom: By offering greater control over urinary incontinence, incontinence devices help individuals maintain an active lifestyle and engage in various activities without worries.


Effectiveness: Many users have experienced a significant reduction in urine leaks and an improvement in their quality of life after using penile devices.


Usually, these devices are safe and effective. However, none of the penile compression devices cause sustained irritation or  impaired blood flow , and generally, patients yield good recovery around 40 minutes after the removal of the devices. [ 2 ]  It is recommended to de-clamp these devices at a regular interval of four hours. [ 1 ]
In the instruction manuals, manufacturers allow continuous use of penis clamps and recommend repositioning them every 2-3 hours (each time after urination).  [ 3 ]
 [ 4 ]
 [ 5 ]


Customers should not buy this type of health products on non-specialized websites. Patients may incur serious risks. Urinary clamps imported directly from Asia may not have passed the necessary medical checks.


A  penis extender  is an external  medical device  with tentative evidence as of 2019 for  Peyronie's disease . It acts as a  mechanical ,  traction  device that stretches the  human penis  in the flaccid state to make it longer. [ 1 ]


Penis extenders usually have a  plastic  ring that sits at the base of a  flaccid penis , and another ring before the  glans penis , with a traction device that runs along the sides of the organ. The wearer adjusts springs, which pull the  penile shaft  with the intention of stretching the flaccid penis to become longer. [ 1 ]


There is tentative evidence for use in  Peyronie's disease . [ 1 ]  As of 2019, studies have been small in size; many had difficulty carrying out the treatment during the study period, and people were not blinded to the treatment that they were receiving. [ 1 ]


Adverse effects are not extensively reported in the literature, and they are usually mild and self-limiting, in part caused by lack of patient compliance with penile traction therapy (PTT). The most commonly reported symptoms with PTT include  pain ,  erythema ,  ecchymoses , and  pruritus . Another reported symptom was  edema  to the  pubic bone , which is associated with vigorous usage. All of these adverse events are generally self-limited and resolve with discontinuation of PTT. [ 1 ]  Seek advice on  how to use the penis extender  safely, and correctly.


It should not be used if penile wounds, lacerations, or infected zones have not fully healed, and by those suffering certain diseases or disorders. [ 2 ]  Aggressive or incorrect uses of penis extenders can cause damage to skin and blood vessels, among other possible issues. [ 3 ]


The  penrig  is a  unit  of  tumescence , specifically for the tumescence of the human  penis . It is defined as the tumescence that will raise 100  grams  of penile tissue through one millimetre. [ 1 ] [ 2 ] [ 3 ]  The word is formed from PENis RIGidity.


Perineology  is a speciality dealing with the functional troubles of the three axes ( urological ,  gynaecological  and  coloproctological ) of the female  perineum . [ 1 ]  The perineologist takes a  holistic approach , using defect-specific and mini-invasive treatments.


The word perineology represents a  neologism . It was invented for the occasion of the 1st International Symposium on Perineology, held in  Venice  in 1990 to reflect an integrated view of the anatomy, physiology and pathology of the pelvic floor. [ 2 ]  It was popularized by the Italian journal Rivista Italiana di Colon-Proctologia. [ 3 ]


Some physicians in France and Italy prefer to use the broader term “pelviperineology”, which reflect a broader multidisciplinary approach to all the aspects of the management of the pelvic floor. [ 4 ]


In 2010, an International Society for Pelviperineology was formed. [ 5 ]


Postorgasmic illness syndrome  ( POIS ) is a  syndrome  in which human males have chronic physical and cognitive symptoms following  ejaculation . [ 1 ]  The symptoms usually onset within seconds, minutes, or hours, and last for up to a week. [ 1 ]  The cause and prevalence are unknown; [ 2 ]  it is considered a  rare disease . [ 3 ]


The distinguishing characteristics of POIS are:


POIS symptoms, which are called a "POIS attack", [ 1 ]  can include some combination of the following: cognitive dysfunction,  aphasia , severe  muscle pain  throughout the body, severe  fatigue , weakness, and flu-like or allergy-like symptoms, [ 4 ]  such as sneezing, itchy eyes, and nasal irritation. [ 5 ] [ 2 ] [ 6 ]  Additional symptoms include headache, dizziness, lightheadedness, extreme hunger, sensory and motor problems, intense discomfort, irritability,  anxiety ,  gastrointestinal  disturbances, craving for relief, susceptibility to nervous system stresses, depressed mood, and difficulty communicating, remembering words, reading and retaining information, concentrating, and socializing. [ 5 ] [ 7 ]  Affected individuals may also experience intense warmth or cold. [ 4 ]  An online anonymous self-report study found that 80% of respondents always experienced the symptom cluster involving fatigue, insomnia, irritation, and concentration difficulties. [ 8 ]


The symptoms usually begin within 30 minutes of  ejaculation , [ 5 ]  and can last for several days, sometimes up to a week. [ 4 ]  In some cases, symptoms may be delayed by 2 to 3 days or may last up to 2 weeks. [ 9 ]


In some men, the onset of POIS is in puberty, while in others, the onset is later in life. [ 10 ]  POIS that is manifest from the first ejaculations in adolescence is called  primary type ; POIS that starts later in life is called  secondary type . [ 1 ]


Many individuals with POIS report lifelong  premature ejaculation , with  intravaginal ejaculation latency time  (IELT) of less than one minute. [ 1 ] [ 6 ]


The 7 clusters of symptoms of criterion 1: [ 10 ]


POIS has been called by a number of other names, including "postejaculatory syndrome", [ 4 ]  "postorgasm illness syndrome", [ 11 ]  "post ejaculation sickness", [ 12 ]  and "post orgasmic sick syndrome". [ 3 ]


Dhat syndrome  is a condition ,  N. N. Wig  first coined the term and described in 1960 in India, [ 13 ]  with symptoms similar to POIS. [ 11 ]  Dhat syndrome is thought to be a  culture-bound   psychiatric  condition and is treated with  cognitive behavioral therapy  along with anti-anxiety and antidepressant drugs. [ 14 ]


Post-coital tristesse  (PCT) is a feeling of  melancholy  and  anxiety  after sexual intercourse that lasts anywhere from five minutes to two hours. PCT, which affects both men and women, occurs only after sexual intercourse and does not require an orgasm to occur, and in that its effects are primarily emotional rather than physiological. By contrast, POIS affects only men, consists primarily of physiological symptoms that are triggered by ejaculation and that can last, in some people, for up to a week. While PCT and POIS are distinct conditions, some doctors speculate that they could be related. [ 11 ]


An array of more subtle and lingering symptoms after orgasm, which do not constitute POIS, may contribute to habituation between mates. They may show up as restlessness, irritability, increased sexual frustration, apathy, sluggishness, neediness, dissatisfaction with a mate, or weepiness [ 15 ]  over the days or weeks after intense sexual stimulation. Such phenomena may be part of  human mating physiology  itself.


Sexual headache  is a distinct condition characterized by headaches that usually begin before or during orgasm. [ 16 ]


The cause of POIS is unknown. Some doctors hypothesize that POIS is caused by an  auto-immune reaction . [ 17 ]  Other doctors suspect a  hormone imbalance  as the cause. Different causes have also been proposed. None of the proposed causes can fully explain the disease.


According to one hypothesis, "POIS is caused by  Type-I  and  Type-IV  allergy to the males' own semen". [ 1 ] [ 18 ] [ 19 ]  This was conditioned by another study stating " IgE -mediated semen allergy in men may not be the potential mechanism of POIS". [ 6 ]


Alternatively, POIS could be caused by an auto-immune reaction not to semen, but to a different substance released during ejaculation, such as  cytokines . [ 11 ]


According to another hypothesis, POIS is caused by a hormone imbalance, such as low  progesterone , [ medical citation needed ]  low  cortisol , low  testosterone , elevated  prolactin ,  hypothyroidism , or low  DHEA . [ 20 ]


POIS could be caused by a defect in  neurosteroid  precursor synthesis. If so, the same treatment may not be effective for all individuals. Different individuals could have different missing precursors leading to a deficiency of the same neurosteroid, causing similar symptoms. [ medical citation needed ]


The majority of POIS symptoms like fatigue, muscle pains, sweating, mood disturbances, irritability, and poor concentration are also caused by  withdrawal  from different drug classes [ 21 ]  and natural reinforcers. [ 22 ]  It is  unknown whether there is a relationship between  hypersexuality ,  pornography addiction ,  compulsive sexual behavior  and POIS. Some evidence indicates that POIS patients have a history of excessive masturbation, suggesting that POIS could be a consequence of sex addiction. There is anecdotal evidence on porn addiction internet forums, that many men experience POIS like symptoms after ejaculation. [ 23 ]


POIS could be caused by  hyperglycemia [ 20 ]  or by chemical imbalances in the brain. [ 24 ]


Sexual activity for the first time  may set the stage for an associated  asthma  attack or may aggravate pre-existing asthma. Intense emotional stimuli during sexual intercourse can lead to autonomic imbalance with parasympathetic over-reactivity, releasing  mast cell  mediators that can provoke postcoital asthma and / or  rhinitis  in these patients. [ 25 ]


It is also possible that the causes of POIS are different in different individuals. POIS could represent "a spectrum of syndromes of differing" causes. [ 11 ]


None of the proposed causes for POIS can fully explain the connection between POIS and  lifelong premature ejaculation . [ 26 ]


There is no generally agreed upon diagnostic criteria for POIS. One group has developed five preliminary criteria for diagnosing POIS. These are:


POIS is prone to being erroneously ascribed to psychological factors such as  hypochondriasis  or  somatic symptom disorder . [ 4 ]


An online survey study suggested that only a small number of self-reported POIS fulfill entirely the five criteria. This study proposed to change the Criterion 3 with “In at least one ejaculatory setting (sex, masturbation, or nocturnal emission), symptoms occur after all or almost all ejaculations.” [ 8 ]


There is no standard method of treating or managing POIS. Patients need to be thoroughly examined in an attempt to find the causes of their POIS symptoms, which are often difficult to determine, and which vary across patients. Once a cause is hypothesized, an appropriate treatment can be attempted. At times, more than one treatment is attempted, until one that works is found. [ citation needed ]


Affected individuals typically avoid sexual activity, [ 4 ]  especially ejaculation, [ 1 ]  or schedule it for times when they can rest and recover for several days afterwards. [ 5 ]  In case  post-coital tristesse  (PCT) is suspected, patients could be treated with  selective serotonin reuptake inhibitors . [ 11 ] [ 24 ]


In one patient, the POIS symptoms were so severe, that he decided to undergo removal of the testicles, prostate, and seminal vesicles in order to relieve them. The POIS symptoms were cured by this. [ 27 ]


Another patient, in whom POIS was suspected to be caused by cytokine release, was successfully treated with  nonsteroidal anti-inflammatory drugs  (NSAIDs) just prior to and for a day or two after ejaculation. The patient took  diclofenac  75 mg 1 to 2 hours prior to sexual activity with orgasm, and continued twice daily for 24 to 48 hours. [ 11 ]


One POIS patient with  erectile dysfunction  and  premature ejaculation  had much lower severity of symptoms on those occasions when he was able to maintain penile erection long enough to achieve vaginal penetration and ejaculate inside his partner. The patient took  tadalafil  to treat his erectile dysfunction and premature ejaculation. This increased the number of occasions on which he was able to ejaculate inside his partner, and decreased the number of occasions on which he experienced POIS symptoms. This patient is thought to have  Dhat syndrome  rather than true POIS. [ 11 ]


Two patients, in whom POIS was suspected to be caused by auto-immune reaction to their own semen, were successfully treated by  allergen immunotherapy  with their own autologous semen. They were given multiple subcutaneous injections of their own semen for three years. [ 1 ]  Treatment with autologous semen "might take 3 to 5 years before any clinically relevant symptom reduction would become manifest". [ 1 ]


Treatments are not always successful, especially when the cause of POIS in a particular patient has not been determined. In one patient, all of whose  routine laboratory tests  were normal, the following were attempted, all without success:  ibuprofen , 400 mg on demand;  tramadol  50 mg one hour pre-coitally; and  escitalopram  10 mg daily at bedtime for 3 months. [ 20 ]


The prevalence of POIS is unknown. [ 2 ]  POIS is listed as a  rare disease  by the American  National Institutes of Health [ 3 ]  and the European  Orphanet . [ 28 ]  It is thought to be underdiagnosed and underreported. [ 7 ]  POIS seems to affect mostly men from around the world, of various ages and relationship statuses. [ 8 ]


It is possible that a similar disease exists in women, though, as of 2016, there is only one documented female patient. [ 1 ]


2ZCH ,  2ZCK ,  2ZCL ,  3QUM


NP_001025218 NP_001025219 NP_001639


Prostate-specific antigen  ( PSA ), also known as  gamma-seminoprotein  or  kallikrein-3  ( KLK3 ), P-30 antigen, is a  glycoprotein   enzyme  encoded in humans by the  KLK3   gene . PSA is a member of the  kallikrein -related  peptidase  family and is secreted by the  epithelial cells  of the  prostate  gland in men and the  paraurethral glands  in women. [ 5 ]


PSA is produced for the  ejaculate , where it liquefies  semen  in the seminal coagulum and allows  sperm  to swim freely. [ 6 ]  It is also believed to be instrumental in dissolving  cervical mucus , allowing the entry of sperm into the  uterus . [ 7 ]


PSA is present in small quantities in the  serum  of men with healthy prostates, but is often elevated in the presence of  prostate cancer  or other prostate disorders. [ 8 ]  PSA is not uniquely an indicator of prostate cancer, but may also detect  prostatitis  or  benign prostatic hyperplasia . [ 9 ]


Clinical practice guidelines  for prostate cancer  screening  vary and are controversial, in part due to uncertainty as to whether the benefits of screening ultimately outweigh the risks of  overdiagnosis  and overtreatment. [ 10 ]  In the United States, the  Food and Drug Administration  (FDA) has approved the PSA test for annual screening of prostate cancer in men of age 50 and older. [ medical citation needed ]  The patient is required to be informed of the risks and benefits of PSA testing prior to performing the test. [ medical citation needed ]


In the United Kingdom, the  National Health Service  (NHS) as of 2018 [update]  does not mandate, nor advise for PSA test, but allows patients to decide based on their doctor's advice. [ 11 ]  The NHS does not offer general PSA screening, for similar reasons. [ 12 ]


PSA levels between 4 and 10   ng/mL (nanograms per milliliter) are considered to be suspicious, and consideration should be given to confirming the abnormal PSA with a repeat test. If indicated,  prostate biopsy  is performed to obtain a tissue sample for histopathological analysis.  [ citation needed ]


While PSA testing may help 1 in 1,000 avoid death due to prostate cancer, 4 to 5 in 1,000 would die from prostate cancer after 10 years even with screening. This means that PSA screening may reduce mortality from prostate cancer by up to 25%. Expected harms include anxiety for 100–120 receiving false positives, biopsy pain, and other complications from biopsy for false positive tests. [ medical citation needed ]


Use of PSA screening tests is also controversial due to questionable test accuracy. The screening can present abnormal results even when a man does not have cancer (known as a  false-positive  result ), or normal results even when a man does have cancer (known as a  false-negative  result ). [ 13 ]  False-positive test results can cause confusion and anxiety in men, and can lead to unnecessary prostate  biopsies , a procedure which causes risk of pain, infection, and  hemorrhage . False-negative results can give men a false sense of security, though they may actually have cancer. [ medical citation needed ]


Of those found to have prostate cancer, overtreatment is common because most cases of prostate cancer are not expected to cause any symptoms due to low rate of growth of the prostate tumor. Therefore, many will experience the side effects of treatment, such as for every 1000 men screened, 29 will experience erectile dysfunction, 18 will develop urinary incontinence, two  will have serious cardiovascular events, one will develop pulmonary embolus or deep venous thrombosis, and one perioperative death. [ failed verification ]  Since the expected harms relative to risk of death are perceived by patients as minimal, men found to have prostate cancer usually (up to 90% of cases) elect to receive treatment. [ 14 ] [ 15 ] [ 16 ]


Men with prostate cancer may be characterized as low, intermediate, or high risk for having/developing metastatic disease or dying of prostate cancer. PSA level is one of three variables on which the risk stratification is based; the others are the grade of prostate cancer ( Gleason grading system ) and the stage of cancer based on physical examination and imaging studies. D'Amico criteria for each risk category are: [ 17 ]


Given the relative simplicity of the 1998 D'Amico criteria (above), other predictive models of risk stratification based on  mathematical probability  constructs exist or have been proposed to allow for better matching of treatment decisions with disease features. [ 18 ]
Studies are being conducted into the incorporation of multiparametric  MRI  imaging results into  nomograms  that rely on PSA, Gleason grade, and tumor stage. [ 19 ]


PSA levels are monitored periodically (e.g., every 6–36 months) after treatment for prostate cancer – more frequently in patients with high-risk disease, less frequently in patients with lower-risk disease. If surgical therapy (i.e., radical prostatectomy) is successful at removing all prostate tissue (and prostate cancer), PSA becomes undetectable within a few weeks. A subsequent rise in PSA level above 0.2   ng/mL [ 20 ]  L [ disputed  –  discuss ]  is generally regarded as evidence of recurrent prostate cancer after a radical prostatectomy; less commonly, it may simply indicate residual benign prostate tissue. [ citation needed ]


Following radiation therapy of any type for prostate cancer, some PSA levels might be detected, even when the treatment ultimately proves to be successful. This makes  interpreting the relationship between PSA levels and recurrence/persistence of prostate cancer after radiation therapy more difficult. PSA levels may continue to decrease for several years after radiation therapy. The lowest level is referred to as the PSA nadir. A subsequent increase in PSA levels by 2.0   ng/mL [ disputed  –  discuss ]  above the nadir is the currently accepted definition of prostate cancer recurrence after radiation therapy. [ citation needed ]


Recurrent prostate cancer detected by a rise in PSA levels after curative treatment is referred to as a " biochemical recurrence ". The likelihood of developing recurrent prostate cancer after curative treatment is related to the pre-operative variables described in the preceding section (PSA level and grade/stage of cancer). Low-risk cancers are the least likely to recur, but they are also the least likely to have required treatment in the first place. [ citation needed ]


PSA levels increase in the setting of prostate infection/inflammation (prostatitis), often markedly (> 100).


PSA was first identified by researchers attempting to find a substance in seminal fluid that would aid in the investigation of rape cases. [ 21 ]  PSA is used to indicate the presence of  semen  in forensic  serology . [ 22 ]  The semen of adult males has PSA levels far in excess of those found in other tissues; therefore, a high level of PSA found in a sample is an indicator that semen may be present. Because PSA is a  biomarker  that is expressed independently of  spermatozoa , it remains useful in identifying semen from  vasectomized  and  azoospermic  males. [ 23 ]


PSA can also be found at low levels in other body fluids, such as urine and breast milk, thus setting a high minimum threshold of interpretation to rule out  false positive  results and conclusively state that semen is present. [ 24 ]  While traditional tests such as crossover  electrophoresis  have a sufficiently low sensitivity to detect only seminal PSA, newer diagnostics tests developed from clinical  prostate cancer screening  methods have lowered the threshold of detection down to 4   ng/mL. [ 25 ]  This level of antigen has been shown to be present in the peripheral blood of males with prostate cancer, and rarely in female urine samples and breast milk. [ 24 ]


PSA is produced in the  epithelial  cells of the prostate, and can be demonstrated in biopsy samples or other  histological  specimens using  immunohistochemistry . Disruption of this epithelium, for example in inflammation or  benign prostatic hyperplasia , may lead to some diffusion of the antigen into the tissue around the epithelium, and is the cause of elevated blood levels of PSA in these conditions. [ 26 ]


More significantly, PSA remains present in prostate cells after they become malignant. Prostate cancer cells generally have variable or weak staining for PSA, due to the disruption of their normal functioning. Thus, individual prostate cancer cells produce less PSA than healthy cells; the raised serum levels in prostate cancer patients is due to the greatly increased number of such cells, not their individual activity. In most cases of prostate cancer, though, the cells remain positive for the antigen, which can then be used to identify  metastasis . Since some high-grade prostate cancers may be entirely negative for PSA, however, histological analysis to identify such cases usually uses PSA in combination with other antibodies, such as  prostatic acid phosphatase  and  CD57 . [ 26 ]


The physiological function of KLK3 is the dissolution of the coagulum, the sperm-entrapping gel composed of  semenogelins  and  fibronectin . Its proteolytic action is effective in liquefying the coagulum so that the sperm can be liberated. The activity of PSA is well regulated. In the prostate, it is present as an inactive pro-form, which is activated through the action of  KLK2 , another kallikrein-related peptidase. In the prostate, zinc ion concentrations are 10 times higher than in other bodily fluids. Zinc ions have a strong inhibitory effect on the activity of PSA and on that of KLK2, so that PSA is totally inactive. [ 27 ]


Further regulation is achieved through pH variations. Although its activity is increased by higher pH, the inhibitory effect of zinc also increases. The pH of semen is slightly alkaline and the concentrations of zinc are high. On ejaculation, semen is exposed to the acidic pH of the  vagina , due to the presence of  lactic acid . In fertile couples, the final vaginal pH after coitus approaches the 6-7 levels, which coincides well with reduced zinc inhibition of PSA. At these pH levels, the reduced PSA activity is countered by a decrease in zinc inhibition. Thus, the coagulum is slowly liquefied, releasing the sperm in a well-regulated manner. [ citation needed ]


Prostate-specific antigen (PSA, also known as kallikrein III, seminin, semenogelase, γ-seminoprotein and P-30 antigen) is a 34- kD   glycoprotein  produced almost exclusively by the  prostate gland . It is a  serine protease  ( EC   3.4.21.77 )  enzyme , the  gene  of which is located on the 19th  chromosome  (19q13) in humans. [ 28 ]


The discovery of prostate-specific antigen (PSA) is beset with controversy; as PSA is present in prostatic tissue and semen, it was independently discovered and given different names, thus adding to the controversy. [ 29 ]


Flocks was the first to experiment with antigens in the prostate [ 30 ]  and 10 years later  Ablin  reported the presence of precipitation antigens in the prostate. [ 31 ]


In 1971, Mitsuwo Hara characterized a unique protein in the semen fluid, gamma-seminoprotein. Li and Beling, in 1973, isolated a protein, E1, from human semen in an attempt to find a novel method to achieve fertility control. [ 32 ] [ 33 ]


In 1978, Sensabaugh identified semen-specific protein p30, but proved that it was similar to E1 protein, and that prostate was the source. [ 34 ]  In 1979, Wang purified a tissue-specific antigen from the prostate ('prostate antigen'). [ 35 ]


PSA was first measured quantitatively in the blood by Papsidero in 1980, [ 36 ]  and Stamey carried out the initial work on the clinical use of PSA as a marker of prostate cancer. [ 29 ]


PSA is normally present in the  blood  at very low levels. The  reference range  of less than 4   ng/mL for the first commercial PSA test, the Hybritech Tandem-R PSA test released in February 1986, was based on a study that found 99% of 472 apparently healthy men had a total PSA level below 4   ng/mL. [ 37 ] [ 38 ] [ 39 ] [ 40 ] [ 41 ] [ 42 ] [ 43 ] [ 44 ]


Increased levels of PSA may suggest the presence of prostate cancer. However, prostate cancer can also be present in the complete absence of an elevated PSA level, in which case the test result would be a  false negative . [ 45 ]


Obesity  has been reported to reduce serum PSA levels. [ 46 ]  Delayed early detection may partially explain worse outcomes in obese men with early prostate cancer. [ 47 ]  After treatment, higher BMI also correlates to higher risk of recurrence. [ 48 ]


PSA levels can be also increased by  prostatitis , irritation,  benign prostatic hyperplasia  (BPH), and recent ejaculation, [ 49 ] [ 50 ]  producing a  false positive  result. Digital  rectal examination  (DRE) has been shown in several studies [ 51 ] [ 52 ] [ 53 ] [ 54 ]  to produce an increase in PSA. However, the effect is clinically insignificant, since DRE causes the most substantial increases in patients with PSA levels already elevated over 4.0   ng/mL. PSA levels are higher during the summer than during the rest of the year. [ 55 ] [ 56 ]


The "normal"  reference ranges  for prostate-specific antigen increase with age, as do the usual ranges in cancer (per associated table). [ 57 ] [ 58 ]


Despite earlier findings, [ 59 ]  recent research suggests that the rate of increase of PSA (e.g. >0.35   ng/mL/yr, the 'PSA velocity' [ 60 ] ) is not a more specific marker for prostate cancer than the serum level of PSA. [ 61 ]


However, the PSA rate of rise may have value in prostate cancer prognosis. Men with prostate cancer whose PSA level increased by more than 2.0   ng per milliliter during the year before the diagnosis of prostate cancer have a higher risk of death from prostate cancer despite undergoing  radical prostatectomy . [ 62 ]  PSA velocity (PSAV) was found in a 2008 study to be more useful than the PSA doubling time (PSA DT) to help identify those men with life-threatening disease before start of treatment. [ 63 ]


Men who are known to be at risk for prostate cancer, and who decide to plot their PSA values as a function of time (i.e., years), may choose to use a  semi-log plot . An exponential growth in PSA values appears as a straight line [ 64 ]  on a semi-log plot, so that a new PSA value significantly above the straight line signals a  switch  to a new and significantly higher growth rate, [ 64 ]  i.e., a higher PSA velocity.


Most PSA in the blood is bound to serum proteins. A small amount is not protein-bound and is called 'free PSA'. In men with prostate cancer, the ratio of free (unbound) PSA to total PSA is decreased. The risk of cancer increases if the free to total ratio is less than 25%. (See graph) The lower the ratio is, the greater the probability of prostate cancer. Measuring the ratio of free to total PSA appears to be particularly promising for eliminating unnecessary  biopsies  in men with PSA levels between 4 and 10   ng/mL. [ 66 ]  However, both total and free PSA increase immediately after ejaculation, returning slowly to baseline levels within 24 hours. [ 49 ]


The PSA test in 1994 failed to differentiate between prostate cancer and benign prostate hyperplasia (BPH) and the commercial assay kits for PSA did not provide correct PSA values. [ 67 ]  Thus with the introduction of the ratio of free-to-total PSA, the reliability of the test has improved. Measuring the activity of the enzyme could add to the ratio of free-to-total PSA and further improve the diagnostic value of test. [ 68 ]  Proteolytically active PSA has been shown to have an anti-angiogenic effect  [ 69 ]  and certain inactive subforms may be associated with prostate cancer, as shown by MAb 5D3D11, an antibody able to detect forms abundantly represented in sera from cancer patients. [ 70 ]
The presence of inactive proenzyme forms of PSA is another potential indicator of disease. [ 71 ]


PSA exists in serum in the free (unbound) form and in a complex with  alpha 1-antichymotrypsin ; research has been conducted to see if measurements of complexed PSA are more specific and sensitive biomarkers for prostate cancer than other approaches. [ 72 ] [ 73 ]


The term prostate-specific antigen is a  misnomer : it is an  antigen  but is not specific to the prostate. Although present in large amounts in prostatic tissue and semen, it has been detected in other body fluids and tissues. [ 24 ]


In women, PSA is found in  female ejaculate  at concentrations roughly equal to that found in male semen. [ 5 ]  Other than semen and female ejaculate, the greatest concentrations of PSA in biological fluids are detected in breast milk and amniotic fluid. Low concentrations of PSA have been identified in the urethral glands, endometrium, normal breast tissue and salivary gland tissue. PSA also is found in the serum of women with breast, lung, or uterine cancer and in some patients with renal cancer. [ 74 ]


Tissue samples can be stained for the presence of PSA in order to determine the origin of malignant cells that have metastasized. [ 75 ]


Prostate-specific antigen has been shown to  interact  with  protein C inhibitor . [ 76 ] [ 77 ]
Prostate-specific antigen interacts with and activates the vascular endothelial growth factors  VEGF-C  and  VEGF-D , which are involved in tumor  angiogenesis  and in the lymphatic  metastasis  of tumors. [ 78 ]


Sexual health clinics  specialize in the prevention and treatment of  sexually transmitted infections .


Sexual health clinics are also called  sexually transmitted disease  (STD) clinics ,  sexually transmitted infection (STI) clinics ,  venereal disease (VD) clinics , or  genitourinary medicine  (GUM) clinics . [ citation needed ]


Sexual health clinics differ from  reproductive health  and  family planning  clinics. Sexual health clinics offer only some reproductive health services. Reproductive health clinics, such as  Planned Parenthood , offer most of the services of sexual health clinics. [ citation needed ]


Sexual health clinics provide some or all of the following: [ citation needed ]


Many clinics provide vaccinations to prevent  infections  from the  hepatitis A  and  B   viruses . [ 1 ]
Young women may receive vaccinations to prevent infection from some strains of the  human papillomavirus  (HPV). [ citation needed ]


Many clinics provide  interpreting  for the hearing impaired or speakers of other languages. [ citation needed ]


Many clinics will help patients tell their sexual contacts if they have a sexually transmitted infection, anonymously if needed. [ 2 ]


Public governmental and  non-profit  clinics often provide services for free or adjust the fee based on a patient's ability to pay.
Sexual health clinics often offer services without appointments. Some clinics open evenings or weekends. Some clinics have separate hours or facilities for men and women. Some clinics serve only specific populations such as women, men,  MSM ,  youths ,  LGBT , ethnic groups, the poor, or students. [ citation needed ]


With the patient's  consent , a  clinician  will inspect the patient visually and by touch. If needed, the clinician will take samples to  test  for  sexually transmitted infections . [ citation needed ]


In a private room or space, the patient will partially undress. [ citation needed ]


The clinician may inspect the patient's: [ citation needed ]


The clinician may swab the patient's:


The clinician may take small blood samples by  pricking a finger  or from a  vein [ 4 ]  to test for  HIV ,  syphilis , and possibly  herpes [ 5 ]  and  hepatitis C . [ 6 ] [ 7 ] [ 8 ]


The clinician may ask for a small  urine  sample, given in private, to test for  chlamydia  and possibly  gonorrhea .
The inspections and taking samples do not hurt, but swabbing the urethra and cervix, and a finger prick blood sample feel uncomfortable.
Women will often receive a  pelvic exam , both external and internal, but usually less thorough than a reproductive health exam.
A patient can choose a female or male clinician if available.
A patient can have a  chaperone .
Some clinics have separate hours or facilities for men and women. [ citation needed ]


Medical  confidentiality  is an important part of the  medical ethics  of a  doctor–patient relationship . Sexual health clinics follow local standards of medical confidentiality to protect the privacy of patients. Some clinics provide anonymous services or protect confidentiality by having a patient use a number or a pseudonym. [ 9 ]


Additional privacy protections sometimes apply to matters of sexuality and reproduction, since these areas are sensitive in many cultures. The  diagnosis of HIV/AIDS  has legal restrictions in patient confidentiality, and some clinics use  rapid antibody tests  to provide results to a patient within 30 minutes, without holding the patient's records. [ citation needed ]


In the United States, clinics receiving federal funding from  Medicaid  or  Title X  of the  Public Health Service Act  must treat all patients confidentially. Thus minors can receive services without parental notification or consent. [ 10 ] [ 11 ] [ 12 ]  Additionally, medical records for all patients age 18 and above are strictly confidential under  HIPAA . [ 13 ]


Medical standards of  informed consent  apply to sexual health clinics. A patient needs information about the purposes and consequences of examinations, tests, treatments, and other procedures. A patient may then choose whether to consent to these procedures. [ citation needed ]


A  minor  may consent to receive some or all of the procedures at many sexual health clinics. [ citation needed ]


In  physiology ,  splay  is the difference between urine threshold (the amount of a substance required in the  kidneys  before it appears in the  urine ) and saturation, or T M,  where saturation is the exhausted supply of  renal  reabsorption carriers. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]  In simpler terms, splay is the concentration difference between a substance's maximum renal reabsorption vs. appearance in the urine. [ 6 ]  Splay is usually used in reference to glucose; [ 1 ]  other substances, such as  phosphate , have virtually no splay at all.


The splay in the glucose titration curve is likely a result of both anatomical and kinetic difference


One study found that glucose reabsorption exhibited low splay and another also found that the  titration curves  for glycine showed a large amount of splay whereas those for lysine showed none [ 13 ]  and the kinetics of carrier-mediated glucose transport possibly explains the level of splay in renal titration curves. As splay can be clinically important, patients with proximal tubule disease, mainly caused by hereditary nature and often in children, have a lower threshold but a normal Tm. Therefore, splay is suggested, probably because "some individual cotransporters have a low glucose affinity but maximal transport rate (renal glycosuria). [ 14 ]  Studies also show that if  sulfate  is reabsorbed by a Tm-limited process, it will have low splay and, in animals, the limits of  citrate  concentration normal in the body, citrate titration curves show a large amount of splay therefore a Tm for citrate reabsorption may actually happen. Also, tubular transport is Tm-limited and the reabsorption mechanism being saturated at a plasma concentration more than 20 times than usual shows a low level of splay. [ 13 ]  Renal abnormalities of glucose excretion, causing  glycosuria , [ 15 ]  may happen as either a result of reduced Tm for glucose or because of an abnormally wide range of nephron heterogeneity so splay of the glucose excretion curve is increased. [ 16 ] [ 17 ]  Two causes are also listed for splay: "heteroginicity in glomerular size, proximal tubular length and number of carrier proteins for glucose reabsorption" and variability of TmG nephrons. [ 18 ]  Splay also occurs between 180 and 350 mg/dL %. [ 18 ] [ 19 ] [ 20 ]


The  St Paul's Medal , established by British urologist  Richard Turner-Warwick  in 1989, is awarded annually by the  British Association of Urological Surgeons  (BAUS) for contributions to the surgical field of  urology  by a person from outside of the United Kingdom. Awardees include  Mohamed Ghoneim ,  Mark Soloway ,  Anthony J. Costello ,  Culley C. Carson III ,  Indy Gill , and  Mani Menon . [ 1 ] [ 2 ]


The  St Peter's Medal  is awarded annually by the  British Association of Urological Surgeons  (BAUS) for contributions to the surgical field of  urology .


The medal was designed and produced by sculptor  William Bloye  of the  Birmingham School of Art  and presented to the BAUS in 1948 by  Bernard Joseph Ward , the BAUS's first vice-president. The first medal was awarded in 1949 to  J. B. Macalpine  who was the first to report bladder cancers associated with the  dye  industry. St Peter on the medal is identified by a key engraved on the bible that he holds. On the reverse is a  laurel wreath  within which the recipient's name is engraved, and around the circumference are the names of  Edwin Hurry Fenwick ,  Peter Freyer  and  John Thomson-Walker .


The St Peter's Medal was designed and produced by sculptor  William Bloye  of the  Birmingham School of Art , for the purpose of being awarded to a person who has made significant contributions to the field of  urology  and is a member of the  British Isles  or  Commonwealth . [ 1 ]


The stamping die for the medal was presented to the  British Association of Urological Surgeons  (BAUS) in 1948 by  Bernard Joseph Ward , the BAUS's first vice-president and urologist at Queen Elizabeth Hospital. [ 2 ] [ 3 ] [ 4 ]  The first medal was awarded in 1949 to  J. B. Macalpine  who first reported bladder cancers associated with the  dye  industry. [ 5 ] [ 6 ]  It has subsequently been awarded annually by the BAUS, usually to one recipient, apart from 1951, 1999, 2005, 2006, 2007 and 2014, when there were two recipients. [ 2 ]


The medal is engraved with the names of the three teachers who influenced Bernard Ward:  Edwin Hurry Fenwick ,  Peter Freyer  and  John Thomson-Walker . [ 4 ]  On presenting the medal in 1948, Ward stated in his speech that "although they were individually attached to other hospitals, they all came together in one hospital,  St. Peter's ; and the suggestion therefore was that in order to honour all three of them, we should call it the St. Peter's Medal. [ 4 ]  The hospital, the first urological hospital in Britain, was named after  Saint Peter , whose name derives from the Latin for rock,  petrus , and who was said by Christ to be the foundation upon which the Christian church was to be constructed. [ 7 ] [ 8 ]


St Peter on the medal is identified by the iconography of a key engraved on the bible that he holds. [ 4 ]  On the reverse of the medal is a  laurel wreath , within which the recipient's name is engraved, and around the wreath are the names of Fenwick, Freyer and Thomson-Walker. [ 4 ]


In 1951, the medal was presented for the second time, and for the first time to two recipients, when  Ronald Ogier Ward  and  Terence J. Millin were given the award . [ 9 ]  In 1959 the medal was awarded to  Harold H. Hopkins , a physicist, [ 10 ]  and in 2006 to  Alison Brading , a physiologist. [ 11 ]  Other recipients have included  Sir Michael Woodruff ,  Richard Turner-Warwick ,  John Wickham ,  Howard Kynaston ,  Geoffrey Chisholm ,  John M. Fitzpatrick ,  Roger Kirby  and  Prokar Dasgupta . [ 2 ] [ 12 ]


In 1975 the  International Medical Society of Paraplegia  proposed to offer a similar award based on the BAUS's St Peter's Medal. [ 13 ]


Summer penile syndrome  (also known as 'Lions Mane Penis') [ 1 ]  is a seasonal pediatric medical condition characterized by redness, swelling ( edema ), and itching ( pruritus ) of the penile skin. [ 2 ]


Summer penile syndrome is usually caused by  chigger  bites on the penis, or, more rarely by exposure of the genital region to plants like poison ivy, sumac, and oak. [ 2 ] [ 3 ]  The majority of cases occur in the summer months, with the clothing associated with warmer weather making penis-arachnid and penis-plant contact more likely. [ 1 ]


First line treatments for Summer penile syndrome include oral  antihistamines  and  cold compresses . In extreme cases where the sufferer is in severe pain or is unable to pass urine, systemic  corticosteroids  are considered. [ 3 ]


This cutaneous condition article is a  stub . You can help Wikipedia by  expanding it .


Tubular fluid  is the fluid in the  tubules  of the  kidney . It starts as a  renal ultrafiltrate  in the  glomerulus , changes composition through the  nephron , and ends up as  urine  leaving through the  ureters .


The composition of tubular fluid changes throughout the nephron, from the  proximal tubule  to the  collecting duct  and then as it exits the body, from the ureter.


A  ureteric balloon catheter  is a  balloon catheter  intended for treating  strictures of the ureter . In fact it is a  double J stent  on which a balloon is mounted. It is connected to a delivery device (pusher) to introduce it from the  bladder  into the  ureter .
The system comprises a non-return valve device, and a pusher with a stylet and two ports. [ citation needed ]


The side port is for injecting  contrast agent  to inflate the balloon, while the straight port is for the guidewire. The catheter has a relatively large-diameter central lumen and a shaft of 2 mm (6 Fr.). The balloon is in two sections: a long narrow section or shaft and a larger cranial bulb. The larger cranial bulb prevents distal migration, while the longer narrow section maintains the increased diameter of a predilated stricture in the ureter section.


A guide wire has to be placed in the ureter. After dilatation of the ureteric stricture with a high pressure dilatation balloon the guidewire remains in place to bring in the ureteric balloon catheter. [ citation needed ]


The balloon is inflated by an injection of contrast medium via side port of the pusher and remains in situ while the expanded  urothelium  heals. The stylet is used to detach the balloon catheter from the pusher. During the healing process urine drains through the wide central lumen while the balloon remains inflated. The ureteric balloon catheter may be used in conjunction with a  double J stent  for additional drainage. To remove the catheter after several weeks the balloon is deflated by snipping the distal end of the catheter.
The catheter can then safely be pulled out. [ citation needed ]


The ureteric balloon catheter is intended to cure two major types of diseases:


An intervention according to this Overtoom procedure is significantly less invasive than the alternative treatments. [ citation needed ]


The balloon is not intended to be used in case of obstructions by stones or  malignancies . [ citation needed ]


Ureteric stricture (ureteral stricture)  is the  pathological  narrowing of the  ureter  which may lead to serious complications such as  kidney  failure.


Several conditions have been identified to cause  strictures  such as impacted ureteric stones,  iatrogenic  injuries, tumours and radiotherapy.


Endoscopic   urological  procedures are common with the advancement of medical  technology  which allows endoscopic procedures to be among the main operative modalities in  urology . However,  complications  can occur, and iatrogenic injury is disruption of healthy tissue which might lead to local  inflammation  in the process of healing and scarring which can result in ureteric stricture.


Non-endoscopic open surgical procedures such as colon surgery where the operation field is very close to the adjacent retro peritoneal  ureter is a well-known procedure where ureters can be injured, especially when surgical plans are distorted in conditions such as tethered  colon cancer  or advanced  inflammatory bowel disease . In the same way  gynaecological  operations near the ureters can lead to their injury, one of the common conditions where surgical plans are not clear is the presence of advanced  endometriosis .


Radiotherapy  had been identified as a cause of ureteric strictures formation. Damage occur as a result of both direct and indirect insults such as direct injury to  cell  proteins and  DNA  or  mutation  of the DNA which leads to future insults respectively. [ 1 ]  This is not surprising as in the same way radiotherapy is expected to treat cancer and hence collateral damage can occur hence  it can be challenging to treat as blood supply and vascularity are believed to be affected when stricture repair is intended. [ 2 ]  For instance, Radiotherapy of  cervical cancer  can cause ureteric stricture in 2.2% of patients at 10 years. [ 3 ]


Radiotherapy had been identified as a modality of treatment of several cancers in the pelvis and the abdomen which may lead to ureteric stricture formation among other urological adverse effects too such as radiation induced  cystitis . Among those cancers are; / colon  and  Anorectal  cancer,  cervical cancer ,  endometrial cancer  and  prostate cancer .


Kidney stones  are becoming more common with time, and their incidence is believed to increase recently due to unhealthy diet habits. The passage of kidney stones into ureters might lead to their impaction and the development of local  inflammatory process  around the stone in addition to the obstruction of the  ipsilateral  kidney and build up of pressure manifested as hydronephrosis. Several studies were conducted to find stricture rates which varies from one to another but it seems that modern technology and treatment approaches are minimising the chances for stricture development post impacted stone treatment.


The  symptoms  of ureteric stricture varies from one patient to another, onset;  acute  or  chronic , mode of injury or concurrent complications play a significant role as most other conditions. It can be associated with  ipsilateral  (same side) kidney obstruction and  hydronephrosis , hence loin pain resulting from hydronephrosis and building up of pressure in the renal pelvis from obstructed urine flow which leads to its statics and pain.


Other symptoms related to ureteric strictures can be those related to complications such as recurrent UTI.


Ureteric strictures can be diagnosed using both imaging modalities and under direct vision through endoscopic procedures such as  Ureteroscopy .


Several  radiological studies  can be used to detect such a stricture.  Ultrasound Scans  can show signs of obstruction such as  hydronephrosis , while a  CT scans  can show the same and can locate the stricture or narrowing especially if used with  contrast  (CT Urogram), it can delineate other  pathologies  that might contribute to stricture such as  Tumours  or impacted stones.


Nuclear imaging  plays a significant role to diagnose difficult cases and to evaluate the ipsilateral  kidney function , such as  MAG3  studies. Dynamic imaging are well known to play an essential diagnostic rule too such as  Whitaker test . Overall, national and local guidelines, surgeon preferences and availability of the diagnostic modality plays a rule in choosing the diagnostic modalities used.


Treatment of ureteric strictures varies from one patient to another depending on the level, cause and extent of stricture in addition to patient factors such as comorbidities and preferences. Treatment options include  minimally invasive   palliative  procedures such as  Nephrostomy  tube insertion or  ureteric stents  insertion or  ureteral balloon  catheter dilatation.


Various surgical techniques are employed to restore urine flow or repair damaged ureters when conservative treatments are insufficient. These reconstructive procedures address issues such as obstructions, trauma, surgical injury, or diseases that compromise the integrity of the urinary tract. The choice of technique depends on the nature and extent of the damage, the location of the ureteral defect, and the patient’s overall condition. [ 4 ]  Procedures such as  Rendez-vous  and  reconstructive surgeries  such as  flaps  or using  ileum [ 5 ]  to reconstruct ureters are used and had various success rates. Ureter reimplantation, for example, repositions the ureters to correct flow abnormalities. Surgical techniques such as the psoas hitch procedure involve mobilizing the bladder to bridge a gap in the ureter by securing it to the psoas muscle for added stability. [ 6 ]  The Boari flap technique reshapes part of the bladder wall into a tube to replace a damaged ureter segment, while appendiceal ureter interposition uses the appendix as a substitute for the ureter. For more extensive reconstruction, the ileal ureter approach repurposes a segment of the small intestine (ileum) to create a new channel for urine flow, often draining into an external pouch.


Technology is driving more hope finding more treatment options, laparoscopic assisted robotic techniques are developing and been reported while  tissue engineering  for reconstruction is not developed yet as it is in other urological reconstruction topics. [ 7 ]


A  ureterosigmoidostomy  is a  surgical  procedure wherein the  ureters , which carry urine from the  kidneys , are diverted into the  sigmoid colon . It is performed as a secondary treatment in  bladder cancer  patients who have undergone  cystectomy . Rarely, the cancer can present in children between the ages of 2 & 10 years old as an aggressive  rhabdomyosarcoma , although there have been diagnoses of children as young as 3 months old. The procedure was also used several decades ago as a correctional procedure for patients born with  bladder exstrophy . In the case of some bladder exstrophy patients, occasional bowel  incontinence  (in this case, a mixture of urine and feces similar to diarrhea) at night is one uncontrollable consequence. [ citation needed ]


Another consequence of this procedure is an increased risk of kidney infections ( nephritis ) due to  bacteria  from  faeces  travelling back up the ureters (reflux). Patients are commonly put on oral prophylactic antibiotics to combat infections in the ureteral tract and kidneys, but this can lead to tolerance of the antibiotic. Consequently, the patient can build up tolerance to a large number of oral antibiotics, leading to the need for inpatient administration of IV (intravenous) antibiotics. [ citation needed ]


Additionally, the urine entering the colon can cause diarrhea and salt imbalance due to the  sodium  and  chloride  in the urine.  Urea  levels in the  blood  are higher due to urea crossing the colon wall. In the  large intestine , sodium is swapped for  potassium , and chloride for  bicarbonate . This causes  hypokalaemia  and  acidosis . Many patients take sodium bicarbonate to combat this. [ citation needed ]


Patients with ureterosigmoidostomy have a 100 times greater chance of developing  carcinoma of the colon  after living with the modification for a number of years (an average of 20–30 years after the operation), 24% of patients go on to develop carcinoma of the bowel. [ 1 ]


This operation is no longer popular in many countries, with an  ileal conduit  (where the ureters lead into a loop of  small intestine ) being preferred. However, ureterosigmoidostomy is still popular in developing countries, as the maintenance of an ileal conduit or catheter is seen to be more difficult. [ citation needed ]


A  urethral bulking injection  is a gynecological procedure and medical treatment used to treat involuntary leakage of urine: urinary incontinence in women. Injectional materials are used to control stress incontinence. Bulking agents are injected into the mucosa surrounding the bladder neck and proximal urethra. This reduces the diameter of the urethra and creates resistance to urine leakage. After the procedure, the pressure forcing the urine from the bladder through the urethra is resisted by the addition of the bulking agent in the tissue surrounding the proximal urethra. Most of the time this procedure prevents urinary stress incontinence in women.


A urethral bulking injection is one type of treatment for  incontinence  in women. Urethral bulking injections are considered by a  clinician  when the woman has  urinary sphincter  dysfunction,  urethral hypermobility , persistent stress urinary incontinence after a  urethral sling  or urethropexy, or stress urinary incontinence in women who cannot undergo surgery due to other illnesses or conditions. It restores the ability to retain urine during coughing, laughing and other normal occurrences that increase inter-abdominal pressure [ 1 ]  Some women choose to have urethral bulking injections because they wish to avoid surgery or the use of mesh material. Another reason other treatments may not be chosen include the desire to maintain fertility. Woman who benefit most from this treatment are those who have a stable bladder neck and an inadequate muscle strength of the sphincter muscles that close the urethra. Urethral instability is identified by the angle of the urethra. This can be evaluated when the woman lies on her back and the angle of the urethral is greater than 30° during coughing. Tests are performed to confirm the diagnosis of stress urinary incontinence such as the bladder capacity to hold urine and the strength of the bladder muscle contractions. [ 2 ]


Diagnosis is aided before the procedure by a thorough evaluation of the woman. Information that is gathered prior to the injection includes consists of a medical history and physical exam. The residual, postvoid residual urine determination and urinalysis and urine culture help in the diagnosis. The surgeon will ask the woman to keep a diary of urine output and frequency. The physician may order a urodynamic evaluation to establish the diagnosis of intrinsic sphincter deficiency. A voiding diary and/or a measured voided volume gives an estimate of bladder capacity. A free-flow uroflowmetric examination gives additional information about flow rate, voided time and volume. A cystometrogram will evaluate detrusor over-activity, bladder compliance, bladder capacity, and abdominal (Valsalva) leak pressure. Another diagnostic tool is the urethral pressure profile. This measures the maximum urethral closure strength. The physician will use instrumentation and do a visual examination called a urethroscopic visualization. [ 2 ]


A woman may not be a good candidate for the procedure. Contraindications for this treatment are having a current urinary tract infection, having difficulty emptying the bladder, having a urethral stricture, having a urethral obstruction or having fragile or sensitive tissue where the injections are to be placed. In some women, cancer treatments may have created changes in the urethra, bladder and sphincter muscles which would prevent the success of the treatment. [ 2 ]


These are the most popular urethral bulking agents in the United States [ as of? ]  now that Contigen is no longer available. The ideal bulking material should be non allergic, tissue friendly, not migrate and be long-lasting. However, this has not been found, and despite a prolonged search, nothing financially feasible as yet appeared to be better than the available bulking agents. Urolastic is a new injectable product that seems to be a good candidate to become the ideal product for a minimal invasive and outpatient treatment of stress urinary incontinence since it is not degraded by the body and maintains form. [ citation needed ]


Urethral bulking agents were first used in 1938 and incorporated morrhuate sodium as the injection material. Bovine collagen use began after 1989 and was considered the best example of treatment. All subsequent studies afterwards were compared with this agent. Its use was stopped in 2011. Other bulking agents have been in use since the 1990s. The use of some was discontinued due to complications, the 'unpleasantness' of the procedure and the cost of the procedure. [ 2 ]


Improved materials continue to be investigated. A successful bulking agent should be readily available, non-inflammatory, easy to inject, easy to prepare, efficacious, durable, inexpensive, biocompatible, nonimmunological, long-lasting, non-migrating (the size of the particles should be larger than 80 μm)   adult stem cell injection therapy using autologous muscle-derived stem cells for the regenerative repair of an impaired sphincter is currently at the forefront of incontinence research. The implanted cells fuse with muscle and release trophic factors promoting nerve and muscle integration. Small pilot studies have suggested restoration of the urethral sphincter over several months' time. [ 2 ]


Urethral hypermobility  is a condition of excessive movement of the female  urethra  due to a weakened urogenital diaphragm. It describes the instability of the urethra in relation to the pelvic floor muscles. A weakened  pelvic floor muscle  fails to adequately close the urethra and hence can cause stress  urinary incontinence . This condition may be diagnosed by primary care providers or urologists. Treatment may include  pelvic floor muscle exercises , surgery (e.g.  urethral sling ), or minimally invasive procedures (e.g.  urethral bulking injections ). [ 1 ] [ 2 ]


The urethra is held in place in relationship to the  pelvic bones  and  bladder  by a combination of ligaments, pelvic floor muscles, and surrounding connective tissue known as the urogenital diaphragm. Damage to any of these structures, or the nerves that control them can cause the urethra to be displaced from its normal position or to have increased range of motion. This can result in lack of effective closure of the urethra and thus urinary leakage, especially when pressure from the abdomen is increased during physical exertion and cough, sneeze, or  valsalva maneuvers . [ 3 ]


Changes during pregnancy and physical trauma during childbirth can cause damage to the pubosacral ligament, uterosacral ligament, and pelvic floor muscles, and the connection of the pubic bone itself. Any of these changes may contribute to urethral hypermobility. [ 1 ]


Males have a lower incidence of urethral hypermobility than females, but  prostatectomy  is one risk factor urethral hypermobility and stress incontinence. [ 4 ]


Urethral hypermobility is often diagnosed indirectly by achieving a diagnosis of stress urinary incontinence. This could include ruling out other types of incontinence and other abnormalities, and specific tests for stress incontinence, for example testing for urinary leakage during cough. Specialized testing to further characterize the degree of urethral hypermobility may include  urodynamic testing ,  voiding cystourethrography ,  pelvic ultrasound , and  electromyography . [ 5 ]  These modalities are only recommended for people who experience ongoing symptoms despite an adequate trial of pelvic floor muscle training. [ 6 ]


The first line treatment for urethral hypermobility is  pelvic floor exercises  under supervision of a  physical therapist . However, there is no consensus on which training regiments are most effective, and studies have not determined which mechanisms improve the function of the pelvic floor muscles (e.g. improving reflex action of muscles in response to abdominal pressure vs. increasing urethral closing pressure). [ 1 ] [ 7 ]


Loss of 5-10% of weight has been shown to result in mild improvement in symptoms that was persistent across follow-up periods of 1-3 years. [ 1 ]


Duloxetine  is a medication in the  Serotonin–norepinephrine reuptake inhibitor  class which is approved in Europe for treatment of stress urinary incontinence and used  off-label  in America for the treatment of stress urinary incontinence. [ 1 ]


Several surgical procedures are available to treat urethral hypermobility. These procedures use combinations of sutures, implanted synthetic mesh, and  autotransplanted  tissue to support and reposition the urethra in relation to the pubic bone and other pelvic structures.


Surgical meshes have come to the public attention due to safety concerns with  vaginal mesh used to treat pelvic organ prolapse , however, the urethral sling surgeries have been demonstrated to be highly effective with low risk of adverse events. [ 1 ]


Urethral bulking involves injecting an inert material into the wall of the urethra to relieve the symptoms of urethral hypermobility. This technique is less invasive than surgery with lower risk of adverse events, however it has a lower cure rate for stress incontinence than other methods. [ 1 ]


Lifestyle interventions such as limiting water intake and scheduling urination are not proven to be effective. [ 1 ]


Stem-cell therapy  and  Electrical muscle stimulation  are being explored to assist regeneration of damaged tissue and muscle growth in the urogenital diaphragm. These trials have been explored in animals  in vivo  and  In vitro  studies, but have not yet been explored in humans. [ 8 ]


A  urethral sling  is a device that is surgically implanted to stabilize the pelvic tissues and organs of women. The surgery that implants this device can help treat  urinary incontinence  and uterine prolapse. An alternative treatment to the placement of the urethral sling is  urethral bulking injections . [ 1 ]


Urinary anti-infective agent , also known as urinary  antiseptic , is medication that can eliminate  microorganisms  causing  urinary tract infection  (UTI). UTI can be categorized into two primary types:  cystitis , which refers to lower urinary tract or bladder infection, and  pyelonephritis , which indicates upper urinary tract or kidney infection. [ 1 ]
 Escherichia coli  (E. Coli) is the predominant microbial trigger of UTIs, accounting for 75% to 95% of reported cases. Other  pathogens  such as  Proteus mirabilis ,  Klebsiella pneumoniae , and  Staphylococcus saprophyticus  can also cause UTIs . [ 2 ] [ 3 ]


The use of antimicrobial therapy to treat UTIs started in the 20th century.  Nitrofurantoin ,  trimethoprim-sulfamethoxazole  (TMP/SMX),  fosfomycin , and  pivmecillinam  are currently the first-line agents for  empiric therapy  of simple cystitis. [ 4 ]  On the other hand, the choice of empiric antimicrobial therapy for pyelonephritis depends on the severity of illness, specific  host factors , and the presence of resistant bacteria.  Ceftriaxone  is often considered for  parenteral treatment , while oral or parenteral  fluoroquinolones , such as  levofloxacin  and  ciprofloxacin , are suitable alternatives for treating pyelonephritis. [ 5 ]


Antimicrobial therapy  should be tailored to the individual, considering factors like the severity of illness, specific host factors, and  pathogen resistance  in the local community. [ 1 ]


Urinary antiseptics are medications that target bacteria in the urinary tract. [ 6 ]  They can be divided into two groups:  bactericidal  agents, and  bacteriostatic  agents. These antiseptics help prevent infections by effectively eliminating UTI symptoms through their action on microorganisms. [ 7 ] [ 8 ]


Nitrofurantoin  is regarded as the first-line agent for simple  cystitis , with an efficacy rate ranging from 88% to 92%. [ 9 ]  It can also be a prophylactic agent to prevent long-term UTIs. [ 10 ]  This antibacterial medication is effective against both  gram-positive  and  gram-negative bacteria . [ 11 ]  Nitrofurantoin exhibits its bactericidal activity through various mechanisms, including inhibiting  ribosomal   translation , causing bacterial  DNA damage  and interfering with the  citric acid cycle . However, the specific role of each mechanism remains to be further explored. [ 9 ] [ 11 ]


When nitrofurantoin is metabolized, it converts into a reactive intermediate that attacks bacterial  ribosomes , inhibiting bacterial protein synthesis. [ 9 ] [ 11 ]  This medication is typically taken orally and has minimal systemic absorption, reducing potential side effects. [ 12 ]  Common adverse reactions associated with nitrofurantoin include brown urine discoloration, nausea, vomiting, loss of appetite, rash, and  peripheral neuropathy . [ 13 ]


Fosfomycin  is a  phosphonic acid  bactericidal agent. It is commonly used as the first-line treatment for acute simple cystitis, demonstrating a 91% cure rate. [ 4 ] [ 9 ]  It is administered orally as a single dose; In more complicated UTIs, the dose is adjusted to be repeated every three days to achieve successful eradication. [ 9 ]


The bactericidal effect of fosfomycin is attributed to its capability to inhibit bacterial wall synthesis by inactivating an enzyme called  pyruvyl transferase , which is responsible for microbial cell wall synthesis. [ 9 ]  Fosfomycin acts against gram-positive and  gram-negative  bacteria. Administration of fosfomycin may lead to side effects such as headache, dizziness,  nausea , vomiting, and abdominal cramps. [ 13 ]


Beta-lactam antibiotics  are often considered as a second-line option for treating UTIs due to their lower effectiveness compared to other antibiotics and their potential adverse effects. [ 14 ] [ 15 ]  Commonly used beta-lactam antibiotics for UTIs include  cephalosporins  and  penicillin . By binding to penicillin-binding proteins through their beta-lactam rings, beta-lactam antibiotics disrupt the normal function of these proteins, inhibiting bacterial  cell wall  synthesis, ultimately resulting in cell death. [ 16 ]


Cephalosporins are a subclass of beta-lactam family with broad-spectrum activity against gram-positive and gram-negative bacteria. [ 12 ]  They are categorized into five generations. [ 16 ]  First and third-generation cephalosporins, like  cefalexin  and ceftriaxone, are more commonly used in clinical practice. [ 17 ]   Common adverse effects associated with cephalosporins include  hypersensitivity , rash,  anaphylaxis , and  seizures . [ 12 ]


Penicillin is another widely used subclass that effectively targets various bacteria. [ 18 ]  However, it is not regarded as the first-line treatment for uncomplicated cystitis because of the high prevalence of penicillin-resistant E. coli strains. [ 12 ]  Within the penicillin class, pivmecillinam is considered the first-line empiric treatment for acute cystitis due to its wide spectrum of activity against gram-negative bacteria and its specific efficacy in the urinary tract. It has consistently demonstrated a high cure rate of over 85% for UTIs and a low resistance rate among E. coli strains. [ 4 ] [ 19 ] [ 20 ]  Amoxicillin-clavulanate combination, which enhances the effectiveness of  amoxicillin , is often used as an alternative for cystitis treatment when other options cannot be used. [ 21 ]