Guidelines For The Diagnosis And Treatment Of Chronic Prostatitis/Chronic Pelvic Pain Syndrome Ⅲ

4 Treatment of CP/CPPS comorbidities

4. 1 CP/CPPS

Combined with ED Studies have reported that the prevalence of sexual dysfunction in CP/CPPS is about 62%, of which ED accounts for 29%［145］. The pathogenesis of CP/CPPS combined with ED involves multiple factors:
CP/CPPS patients often develop mental and psychological disorders such as anxiety and depression due to long-term pain, LUTS and other symptoms, which can seriously affect erection and sexual satisfaction［146］; In addition, CP/CPPS combined with ED may also be related to factors such as pelvic floor muscle dysfunction［147］, hypogonadism［148］, and prostate calcification［149］.

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There is still a lack of direct and sufficient evidence-based medical basis for the treatment of CP/CPPS combined with ED. The following points are suggested:

① In the treatment of clinical symptoms such as pain and LUTS related to CP/CPPS, psychotropic drugs can be used at the same time [150-151]. This can not only effectively relieve the patient's pain and LUTS symptoms, but also improve the mental state and quality of life. Studies have reported that α-receptor blockers [152] and pelvic floor muscle relaxation training [153] can improve erectile function while treating CP/CPPS-related symptoms.
② Multiple studies have confirmed that type 5 phosphodiesterase inhibitors combined with α-receptor blockers can effectively improve LUTS and ED problems in BPH patients [154-155]. Tadalafil alone can also relieve BPH/LUTS and ED symptoms at the same time [156].
③ During the treatment of CP/CPPS combined with ED, it is also necessary to pay attention to active health education and psychological counseling for patients, and encourage patients to maintain good eating and sleeping habits and regular sexual life.

4.2 CP/CPPS combined with premature ejaculation
Epidemiological studies in my country have found that the prevalence of premature ejaculation in CP/CPPS patients is as high as 26% [157]. Foreign studies have found that the prevalence of primary or secondary premature ejaculation increases significantly with the severity of pelvic pain in CP/CPPS patients; in patients with moderate to severe pelvic pain symptoms, the prevalence of premature ejaculation can reach 45%, and their PEDT is significantly positively correlated with the NIH-CPSI score [158]; similar findings have been obtained in a number of clinical studies on the Chinese population [159-160]. CP/CPPS has been confirmed to be one of the important organic causes of secondary premature ejaculation [161-163]. Compared with healthy people, patients with primary or secondary premature ejaculation have more significant CP/CPPS symptoms; after treatment of CP/CPPS, the intravaginal ejaculation latency time (IELT) of some patients is significantly prolonged［164-165］.

The specific mechanism of CP/CPPS combined with premature ejaculation is not yet clear. Possible mechanisms include: ① Important causes of premature ejaculation such as mental stress and excessive ideological burden often induce sympathetic nerve excitement, resulting in perineal pain and discomfort, LUTS, ejaculation pain, etc. CP/CPPS Symptoms; CP/CPPS symptoms will aggravate the patient's anxiety and depression, thereby aggravating premature ejaculation [166].

②CP/CPPS may affect the sensation and regulation of the ejaculatory reflex, and sensory impairment is one of the important risk factors for premature ejaculation [167].
③Cytokines/chemokines produced during the onset of CP/CPPS stimulate the prostate and its surrounding nerves, causing a decrease in sexual excitement threshold and changes in the nerve function that regulates the ejaculation reflex, thereby causing or aggravating the symptoms of premature ejaculation [168].
④Animal experiments show that the inflammatory immune response induced by CP/CPPS can significantly up-regulate the expression of NMDA receptors in the paraventricular nucleus, shortening the ejaculation latency by enhancing the sensitivity of the sympathetic nervous system, thereby leading to the occurrence of premature ejaculation. However, the expression of this NMDA receptor is up-regulated. The mechanism requires further study [169].
It is recommended to collect the medical history of premature ejaculation in patients with CP/CPPS, and to routinely screen for CP/CPPS in patients with premature ejaculation [158-159, 165]. For patients who have been diagnosed with CP/CPPS and comorbid premature ejaculation, treatment targeting CP/CPPS should be given priority [163].
When α1-blockers and/or antibiotics are used as well as pelvic floor physical therapy for CP/CPPS, the accompanying symptoms of premature ejaculation can be improved to varying degrees [164, 169]. When simple treatment of CP/CPPS is not effective, it should be combined with targeted treatment of premature ejaculation. The combined use of serotonin reuptake inhibitors can not only significantly improve the symptoms of premature ejaculation, but also relieve symptoms such as anxiety, depression, and physical pain in patients. After patients were treated with the combination, the ejaculation frequency, IELT, PEDT score and NIH-CPSI score were significantly improved [170].

4.3 CP/CPPS combined with male infertility

Among male infertility, the incidence of CP/CPPS ranges from 20% to 80%［171-172］. It is generally believed that the proportion of male infertility caused by CP/CPPS alone is usually less than 5%［171］. CP/CPPS has an adverse effect on semen quality［173］.

Some components of prostatic fluid are involved in regulating fertility-related molecular pathways, involving processes such as controlling ejaculation, regulating semen coagulation and liquefaction, sperm activation and capacitation, and are also related to stimulating gene expression and cellular changes in the female reproductive tract and immune system［58］. Possible mechanisms by which CP/CPPS may affect fertility include: oxidative stress [174-175], inflammatory cytokines [174, 176-178], autoimmune response [179-180], impaired secretory function [181-182], decreased sperm quality [180, 183-184], etc.

For male infertility patients with CP/CPPS symptoms, it is necessary to communicate with the patient carefully and establish a complete medical history. Some patients do not have CP/CPPS symptoms, but laboratory tests show elevated white blood cells in EPS/semen. In this case, a differential diagnosis should be made for type IV prostatitis [41].

Infection and inflammation occur in approximately 15% of male infertile patients. The impact of prostatitis on infertility has been controversial [185]. Some CP/CPPS patients have evidence of prostatitis. It is generally believed that the contact time between sperm and inflammatory cells and inflammatory mediators in prostatic fluid after ejaculation is relatively short. Therefore, the effects of prostatitis or prostatic vesiculitis on sperm quality and male fertility may be fundamentally different from those of epididymitis or orchitis [186].

The treatment of CP/CPPS combined with infertility should focus on eliminating pathogenic microorganisms that may exist in prostatic fluid and semen, improving inflammation and glandular secretion function, and improving sperm quality to enhance fertility.

4.4 CP/CPPS

Combined with anxiety and depression CP/CPSS patients often have a series of mental and psychological problems, including severe anxiety and depression [187-188]; males with depression and anxiety in the general population have higher CP/CPPS symptom scores [189]; antidepressant, anxiety drugs and psychotherapy can effectively improve patients' abnormal emotions and CP/CPPS symptoms [102, 190]. CP/CPPS and depression have some common pathogenesis: potential psychological suggestion, changes in hormone levels [148], production of inflammatory and anti-inflammatory cytokines [191], abnormal neuroendocrine regulation [192], sensitization of the central nervous system related to pain, etc. [193].

Combined with the results of the self-assessment and other-assessment emotional scales, CP/CPPS patients with moderate/severe anxiety, depression or obvious suicidal tendencies are recommended to be transferred to the psychiatric department for treatment first; general patients with anxiety and depression are recommended to receive psychological treatment in addition to drug treatment to reduce the impact of negative emotions on the physical symptoms of the disease. For commonly used psychological treatment methods, please refer to the "3.7 Psychological Treatment" section.

4. 5 CP/CPPS merge

The onset of BPH /LUTS CP /CPPS runs throughout the life of men after puberty; BPH mainly affects middle-aged and elderly people, and the symptoms of BPH /LUTS and CP /CPPS overlap. Chronic inflammation of the prostate is commonly found in patients with BPH/LUTS, and studies have found that the degree of inflammation is weakly correlated with the degree of LUTS symptoms [194].

Among BPH/LUTS people, those who have symptoms such as pelvic pain or discomfort may also have CP/CPPS; among this group of people, if there are no symptoms related to CP/CPPS, but inflammation is found due to prostate biopsy, they are consistent with the diagnosis of type IV prostatitis.

The treatment of CP /CPPS and BPH /LUTS have similar treatment goals, namely reducing symptoms and improving quality of life. BPH /LUTS patients also need to consider removing obstruction and preventing complications. Therefore, when the two diseases coexist, treatment measures should take into account the above goals, and combine physical therapy, surgical treatment, etc. on the basis of general treatment and drug treatment. The treatment methods for CP /CPPS are also applicable to the management of comorbid CP /CPPS and BPH /LUTS. 5α-reductase inhibitors are more effective in CP/CPPS patients with BPH and larger prostate volumes. Surgical treatment is performed only when there is an indication for BPH/LUTS surgery.
Surgery not only relieves urinary tract obstruction, but also drains and eliminates possible prostate inflammation lesions. Perioperative drug therapy is beneficial to reducing complications, promoting postoperative recovery and symptom relief [195-196].

5 Health education for CP/CPPS patients

5.1 Correct understanding of CP/CPPS and its diagnosis and treatment CP/CPPS is a common disease in urology and men's outpatient clinics. It causes long-term pain and urination symptoms in the perineum and pelvis, which may affect sexual function and mental health, thereby seriously affecting the patient's quality of life [145]. Both doctors and patients should realize that although CP/CPPS accompanies some patients for a long time, it will not endanger life and the function of important organs. The cause and pathogenesis of CP/CPPS are not yet clear. Current evidence-based medicine has not confirmed that CP/CPPS is necessarily related to prostate hyperplasia, prostate cancer and infertility.

Due to the lack of correct channels for some patients to obtain medical knowledge, lack of medical knowledge or lack of correct judgment, they cannot bear the psychological distress of CP/CPPS, which affects their sleep, life, study and work. In severe cases, they may develop psychological disorders such as depression and anxiety [197]. Correct understanding of CP/CPPS must be based on timely consultation with doctors, especially listening to the advice of specialists.
Before treatment, doctors need to make a clear diagnosis and correctly treat the disease, and patients need to cooperate patiently. During treatment, doctors should treat patients according to their different symptoms. At the same time, they should advise patients to quit smoking and drinking, avoid spicy food, strengthen their own conditioning, keep a good mood, have a regular daily routine, have a regular sex life, pay attention to keeping warm, and exercise moderately.

5.2 CP/CPPS

Exercise therapy for patients CP/CPPS has a certain relationship with lack of exercise: Lack of exercise means that the sitting and lying time may be prolonged, and long-term sitting can induce CP/CPPS; people who lack exercise have relatively slow blood circulation, causing pelvic congestion, congestion and edema of organs such as the prostate; people who lack exercise have a decline in physical fitness and insufficient resistance to disease; long-term lack of exercise makes the body's internal environment abnormal, and even causes endocrine dysfunction, etc.［198-199］.

It is recommended that CP/CPPS patients perform moderate aerobic exercise to avoid chronic injuries and trauma caused by high-intensity exercise.

5. 3 CP/CPPS

Diet therapy for patients CP/CPPS has a long course and is prone to relapse. If it can be supplemented with diet therapy during the treatment process or recovery period, it will play a positive role in improving the efficacy and preventing recurrence. Inflammation can lead to a decrease in the zinc ion concentration of the prostate, affecting the disease resistance of the prostate. Patients can choose foods with high zinc content such as apples and peanuts.
Patients should pay attention to drinking more water and avoid holding urine for a long time; eat more light and easily digestible foods, and maintain smooth bowel movements.

5. 4 CP/CPPS

Psychological intervention for patients CP/CPPS patients have serious physical and mental burdens, especially patients who are affected by the disease for a long time, are prone to negative emotions, and clinical treatment cannot achieve satisfactory results.

Some patients mistakenly believe that they will be discriminated against if they have prostate diseases, which affects their family life and marital happiness.
Patients should receive psychological counseling from professional physicians in a timely manner. Through full communication between doctors and patients, patients can have a correct understanding of the disease, treat both the body and mind, and improve their condition. Studies have shown that psychological intervention can effectively improve the efficacy and psychological state of CP/CPPS patients who have poor drug and physical therapy effects [200-201].