The disease is classified as either gonococcal urethritis, caused by "Neisseria gonorrhoeae", or non-gonococcal urethritis (NGU), most commonly caused by "Chlamydia trachomatis". NGU, sometimes called nonspecific urethritis (NSU), has both infectious and noninfectious causes.

Urethritis is part of triad of Reiter's Syndrome.

Other causes include:

- Adenoviridae

- Uropathogenic "Escherichia coli" (UPEC)

- Herpes simplex

- Cytomegalovirus

- "Mycoplasma genitalium"

- Reactive arthritis

- "Trichomonas vaginalis"

- "Ureaplasma urealyticum"

- "Methicillin-resistant Staphylococcus aureus"

- "Group B streptococcus"

There are many causes of NGU. This is in part due to the large variety of organisms living in the urinary tract. "Ureaplasma urealyticum" and "Mycoplasma genitalium" are some of the culprits.

NGU is also associated with Reiter's syndrome,in which triad of Arthritis,Conjunctivitis & Urethritis is there.

The most common bacterial cause of NGU is "Chlamydia trachomatis", but it can also be caused by "Ureaplasma urealyticum", "Haemophilus vaginalis", "Mycoplasma genitalium", Mycoplasma hominis, Gardnerella vaginalis, Acinetobacter lwoffi, Ac.calcoclaceticus and "E.coli".

Urethritis is inflammation of the urethra. The most common symptom is painful or difficult urination. It is usually caused by infection with bacteria. The bacterial infection is often sexually transmitted, but not in every instance. Urethritis can be idiopathic.

Research has shown a link between trichomoniasis and two serious sequelae. Data suggest that:

- Trichomoniasis is associated with increased risk of transmission and infection of HIV.

- Trichomoniasis may cause a woman to deliver a low-birth-weight or premature infant.

- The role of trichomonas infection in causing cervical cancer is unclear, although trichomonas infection may be associated with co-infection with high-risk strains of HPV.

- "T. vaginalis" infection in males has been found to cause asymptomatic urethritis and prostatitis. In the prostate, it may create chronic inflammation that may eventually lead to prostate cancer.

In young sexually active women, sexual activity is the cause of 75–90% of bladder infections, with the risk of infection related to the frequency of sex. The term "honeymoon cystitis" has been applied to this phenomenon of frequent UTIs during early marriage. In post-menopausal women, sexual activity does not affect the risk of developing a UTI. Spermicide use, independent of sexual frequency, increases the risk of UTIs. Diaphragm use is also associated. Condom use without spermicide or use of birth control pills does not increase the risk of uncomplicated urinary tract infection.

Women are more prone to UTIs than men because, in females, the urethra is much shorter and closer to the anus. As a woman's estrogen levels decrease with menopause, her risk of urinary tract infections increases due to the loss of protective vaginal flora. Additionally, vaginal atrophy that can sometimes occur after menopause is associated with recurrent urinary tract infections.

Chronic prostatitis in the forms of chronic prostatitis/chronic pelvic pain syndrome and chronic bacterial prostatitis (not acute bacterial prostatitis or asymptomatic inflammatory prostatitis) may cause recurrent urinary tract infections in males. Risk of infections increases as males age. While bacteria is commonly present in the urine of older males this does not appear to affect the risk of urinary tract infections.

Urinary catheterization increases the risk for urinary tract infections. The risk of bacteriuria (bacteria in the urine) is between three and six percent per day and prophylactic antibiotics are not effective in decreasing symptomatic infections. The risk of an associated infection can be decreased by catheterizing only when necessary, using aseptic technique for insertion, and maintaining unobstructed closed drainage of the catheter.

Male scuba divers utilizing condom catheters and female divers utilizing external catching devices for their dry suits are also susceptible to urinary tract infections.

Cervicitis can be caused by any of a number of infections, of which the most common are chlamydia and gonorrhea, with chlamydia accounting for approximately 40% of cases. As many half of pregnant women are asymptomatic with a gonorrhea infection of the cervix. "Trichomonas vaginalis" and herpes simplex are less common causes of cervicitis. There is a consistent association of M. genitalium infection and female reproductive tract syndromes. M. genitalium infection is significantly associated with increased risk of cervicitis.

There were about 58 million cases of trichomoniasis in 2013. It is more common in women (2.7%) than males (1.4%). It is the most common non-viral STI in the U.S., with an estimated 3.7 million prevalent cases and 1.1 million new cases per year. It is estimated that 3% of the general U.S. population is infected, and 7.5-32% of moderate-to-high risk (including incarcerated) populations.

Chlamydia can be transmitted during vaginal, anal, or oral sex or direct contact with infected tissue such as conjunctiva. Chlamydia can also be passed from an infected mother to her baby during vaginal childbirth.

Mucopurulent cervicitis (MPC) is characterized by a purulent or mucopurulent endocervical exudate visible in the endocervical canal or in an endocervical swab specimen. Some specialists also diagnose MPC on the basis of easily induced cervical bleeding. Although some specialists consider an increased number of polymorphonuclear white blood cells on endocervical Gram stain as being useful in the diagnosis of MPC, this criterion has not been standardized, has a low positive-predictive value (PPV), and is not available in some settings. MPC often is without symptoms, but some women have an abnormal vaginal discharge and vaginal bleeding (e.g., after sexual intercourse). MPC can be caused by "Chlamydia trachomatis" or "Neisseria gonorrhoeae"; however, in most cases neither organism can be isolated. MPC can persist despite repeated courses of antimicrobial therapy. Because relapse or reinfection with "C. trachomatis" or "N. gonorrhoeae" usually does not occur in persons with persistent cases of MPC, other non-microbiologic determinants (e.g., inflammation in the zone of ectopy) might be involved.

Patients who have MPC should be tested for "C. trachomatis" and for "N. gonorrhoeae" with the most sensitive and specific test available. However, MPC is not a sensitive predictor of infection with these organisms; most women who have "C. trachomatis" or "N. gonorrhoeae" do not have MPC.

For sexually active women who are not pregnant, screening is recommended in those under 25 and others at risk of infection. Risk factors include a history of chlamydial or other sexually transmitted infection, new or multiple sexual partners, and inconsistent condom use. For pregnant women, guidelines vary: screening women with age or other risk factors is recommended by the U.S. Preventive Services Task Force (USPSTF) (which recommends screening women under 25) and the American Academy of Family Physicians (which recommends screening women aged 25 or younger). The American College of Obstetricians and Gynecologists recommends screening all at risk, while the Centers for Disease Control and Prevention recommend universal screening of pregnant women. The USPSTF acknowledges that in some communities there may be other risk factors for infection, such as ethnicity. Evidence-based recommendations for screening initiation, intervals and termination are currently not possible. For men, the USPSTF concludes evidence is currently insufficient to determine if regular screening of men for chlamydia is beneficial. They recommend regular screening of men who are at increased risk for HIV or syphilis infection.

In the United Kingdom the National Health Service (NHS) aims to:

1. Prevent and control chlamydia infection through early detection and treatment of asymptomatic infection;

2. Reduce onward transmission to sexual partners;

3. Prevent the consequences of untreated infection;

4. Test at least 25 percent of the sexually active under 25 population annually.

5. Retest after treatment.

Regular testing for sexually transmitted infections is encouraged for prevention. The risk of contracting pelvic inflammatory disease can be reduced by the following:

- Using barrier methods such as condoms; see human sexual behavior for other listings.

- Seeking medical attention if you are experiencing symptoms of PID.

- Using hormonal combined contraceptive pills also helps in reducing the chances of PID by thickening the cervical mucosal plug & hence preventing the ascent of causative organisms from the lower genital tract.

- Seeking medical attention after learning that a current or former sex partner has, or might have had a sexually transmitted infection.

- Getting a STI history from your current partner and strongly encouraging they be tested and treated before intercourse.

- Diligence in avoiding vaginal activity, particularly intercourse, after the end of a pregnancy (delivery, miscarriage, or abortion) or certain gynecological procedures, to ensure that the cervix closes.

- Reducing the number of sexual partners.

- Sexual monogamy.

- Abstinence

PID can cause scarring inside the reproductive system, which can later cause serious complications, including chronic pelvic pain, infertility, ectopic pregnancy (the leading cause of pregnancy-related deaths in adult females), and other complications of pregnancy. Occasionally, the infection can spread to in the peritoneum causing inflammation and the formation of scar tissue on the external surface of the liver (Fitz-Hugh–Curtis syndrome).

If symptomatic, testing is recommended. The risk of contracting Micoplasma infection can be reduced by the following:

- Using barrier methods such as condoms

- Seeking medical attention if you are experiencing symptoms suggesting a sexually transmitted infection.

- Seeking medical attention after learning that a current or former sex partner has, or might have had a sexually transmitted infection.

- Getting a STI history from your current partner and insisting they be tested and treated before intercourse.

- Avoiding vaginal activity, particularly intercourse, after the end of a pregnancy (delivery, miscarriage, or abortion) or certain gynecological procedures, to ensure that the cervix closes.

- Abstinence

The main infectious agents are Enterobacteriaceae (such as Escherichia coli and Klebsiella), Neisseria gonorrhoeae and Chlamydia trachomatis.

One study has shown that men with MAGI who have lower serum levels of total testosterone tend to have a more complicated form of MAGI, such as involving more than one site, than those with normal levels.

Neonates, especially if preterm, are susceptible to "M. hominis" infection.

Meningoencephalitis in neonates has been described and M. hominis may be a significant causative agent of neonatal sepsis or meningitis.

"M. hominis" has been associated with chorioamnionits. "M. hominis" is associated with miscarriage.

Potential complications include:

- obstruction of the epididymis

- impairment of spermatogenesis

- impairmentment of sperm function

- induction of sperm auto-antibodies

- dysfunctions of the male accessory glands

These complications can result in

sexual dysfunction and male subfertility.

It had also been associated with a number of diseases in humans, including nonspecific urethritis, and infertility.

Infection in the newborn is accompanied by a strong immune response and is correlated with the need for prolonged mechanical ventilation.

Infection with "U. urealyticum" in pregnancy and birth can be complicated by chorioamnionitis, stillbirth, premature birth, and, in the perinatal period, pneumonia, bronchopulmonary dysplasia and meningitis. "U. urealyticum" has been found to be present in amniotic fluid in women who have had a premature birth with intact fetal membranes.

"U. urealyticum" has been noted as one of the infectious causes of sterile pyuria. It increases the morbidity as a cause of neonatal infections. It is associated with premature birth, preterm rupture of membranes, preterm labor, cesarean section, placental inflammation, congenital pneumonia, bacteremia, meningitis, fetal lung injury and death of infant. "Ureaplasma urealyticum" is associated with miscarriage.

Urethral strictures most commonly result from injury, urethral instrumentation, infection, non-infectious inflammatory conditions of the urethra, and after prior hypospadias surgery. Less common causes include congenital urethral strictures and those resulting from malignancy.

Urethral strictures after blunt trauma can generally be divided into two sub-types;

- Pelvic fracture-associated urethral disruption occurs in as many as 15% of severe pelvic fractures. These injuries are typically managed with suprapubic tube placement and delayed urethroplasty 3 months later. Early endoscopic realignment may be used in select cases instead of a suprapubic tube, but these patients should be monitored closely as vast majority of them will require urethroplasty.

- Blunt trauma to the perineum compresses the bulbar urethra against the pubic symphysis, causing a "crush" injury. These patients are typically treated with suprapubic tube and delayed urethroplasty.

Other specific causes of urethral stricture include:

- Instrumentation (e.g., after transurethral resection of prostate, transurethral resection of bladder tumor, or endoscopic kidney surgery)

- Infection (typically with Gonorrhea)

- Lichen sclerosus

- Surgery to address hypospadias can result in a delayed urethral stricture, even decades after the original surgery.

The use of bioengineered urethral tissue is promising, but still in the early stages. The Wake Forest Institute of Regenerative Medicine has pioneered the first bioengineered human urethra, and in 2006 implanted urethral tissue grown on bioabsorbable scaffolding (approximating the size and shape of the affected areas) in five young (human) males who suffered from congenital defects, physical trauma, or an unspecified disorder necessitating urethral reconstruction. As of March, 2011, all five recipients report the transplants have functioned well.

Odynorgasmia, or painful ejaculation, is a physical syndrome described by pain or burning sensation of the urethra or perineum during or following ejaculation. Causes include infections associated with urethritis, prostatitis, epididymitis, as well as use of anti-depressants.

As with almost all sexually transmitted infections, women are more susceptible to acquiring genital HSV-2 than men. On an annual basis, without the use of antivirals or condoms, the transmission risk of HSV-2 from infected male to female is about 8–11%.

This is believed to be due to the increased exposure of mucosal tissue to potential infection sites. Transmission risk from infected female to male is around 4–5% annually. Suppressive antiviral therapy reduces these risks by 50%. Antivirals also help prevent the development of symptomatic HSV in infection scenarios, meaning the infected partner will be seropositive but symptom-free by about 50%. Condom use also reduces the transmission risk significantly. Condom use is much more effective at preventing male-to-female transmission than "vice versa". Previous HSV-1 infection may reduce the risk for acquisition of HSV-2 infection among women by a factor of three, although the one study that states this has a small sample size of 14 transmissions out of 214 couples.

However, asymptomatic carriers of the HSV-2 virus are still contagious. In many infections, the first symptom people will have of their own infections is the horizontal transmission to a sexual partner or the vertical transmission of neonatal herpes to a newborn at term. Since most asymptomatic individuals are unaware of their infection, they are considered at high risk for spreading HSV.

In October 2011, the anti-HIV drug tenofovir, when used topically in a microbicidal vaginal gel, was reported to reduce herpes virus sexual transmission by 51%.

Following active infection, herpes viruses establish a latent infection in sensory and autonomic ganglia of the nervous system. The double-stranded DNA of the virus is incorporated into the cell physiology by infection of the nucleus of a nerve's cell body. HSV latency is static; no virus is produced; and is controlled by a number of viral genes, including latency-associated transcript.

Many HSV-infected people experience recurrence within the first year of infection. Prodrome precedes development of lesions. Prodromal symptoms include tingling (paresthesia), itching, and pain where lumbosacral nerves innervate the skin. Prodrome may occur as long as several days or as short as a few hours before lesions develop. Beginning antiviral treatment when prodrome is experienced can reduce the appearance and duration of lesions in some individuals. During recurrence, fewer lesions are likely to develop and are less painful and heal faster (within 5–10 days without antiviral treatment) than those occurring during the primary infection. Subsequent outbreaks tend to be periodic or episodic, occurring on average four or five times a year when not using antiviral therapy.

The causes of reactivation are uncertain, but several potential triggers have been documented. A 2009 study showed the protein VP16 plays a key role in reactivation of the dormant virus. Changes in the immune system during menstruation may play a role in HSV-1 reactivation. Concurrent infections, such as viral upper respiratory tract infection or other febrile diseases, can cause outbreaks. Reactivation due to other infections is the likely source of the historic terms 'cold sore' and 'fever blister'.

Other identified triggers include local injury to the face, lips, eyes, or mouth; trauma; surgery; radiotherapy; and exposure to wind, ultraviolet light, or sunlight.

The frequency and severity of recurrent outbreaks vary greatly between people. Some individuals' outbreaks can be quite debilitating, with large, painful lesions persisting for several weeks, while others experience only minor itching or burning for a few days. Some evidence indicates genetics play a role in the frequency of cold sore outbreaks. An area of human chromosome 21 that includes six genes has been linked to frequent oral herpes outbreaks. An immunity to the virus is built over time. Most infected individuals experience fewer outbreaks and outbreak symptoms often become less severe. After several years, some people become perpetually asymptomatic and no longer experience outbreaks, though they may still be contagious to others. Immunocompromised individuals may experience longer, more frequent, and more severe episodes. Antiviral medication has been proven to shorten the frequency and duration of outbreaks. Outbreaks may occur at the original site of the infection or in proximity to nerve endings that reach out from the infected ganglia. In the case of a genital infection, sores can appear at the original site of infection or near the base of the spine, the buttocks, or the back of the thighs.

HSV-2-infected individuals are at higher risk for acquiring HIV when practicing unprotected sex with HIV-positive persons, in particular during an outbreak with active lesions.