Medicine:Sexual dysfunction

From HandWiki
Short description: Difficulty experienced by humans during any stage of normal sexual activity
Sexual dysfunction
Other namesSexual malfunction, sexual disorder
SpecialtySexology, gynecology, andrology

Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction as a "person's inability to participate in a sexual relationship as they would wish".[1] This definition is broad and is subject to many interpretations.[2] A diagnosis of sexual dysfunction under DSM-5 requires a person to feel extreme distress and interpersonal strain for a minimum of six months (except for substance- or medication-induced sexual dysfunction). Sexual dysfunctions can have a profound impact on an individual's perceived quality of sexual life.[3] The term sexual disorder may not only refer to physical sexual dysfunction, but to paraphilias as well; this is sometimes termed disorder of sexual preference.

A thorough sexual history and assessment of general health and other sexual problems (if any) are important in the assessment of sexual dysfunction. This is because sexual dysfunction is usually correlated with other psychiatric issues, such as: mood disorders, eating and anxiety disorders, and even schizophrenia.[4][5][6] Assessing performance anxiety, guilt, stress, and worry are integral to the optimal management of sexual dysfunction. Many of the sexual dysfunctions that are defined are based on the human sexual response cycle as proposed by William H. Masters and Virginia E. Johnson and modified by Helen Singer Kaplan.

Types

Sexual dysfunction disorders may be classified into four categories: sexual desire disorders, arousal disorders, orgasm disorders, and pain disorders. Sexual dysfunctions among men and women are studied in the fields of andrology and gynaecology, respectively.[7]

Sexual desire disorders

Main page: Medicine:Hypoactive sexual desire disorder

Sexual desire disorders or decreased libido are characterized by a lack, or absence for some time, of sexual desire or that of libido for sexual activity or of sexual fantasies. The condition ranges from a general lack of sexual desire, to a lack of sexual desire for the current partner. The condition may have started after a period of normal sexual functioning, or the person may always have had an absence or a lesser intensity of sexual desire.

The causes vary considerably but include a decrease in the production of normal estrogen in women or testosterone in both men and women. Other causes may be ageing, fatigue, pregnancy, medications (such as the SSRIs), or psychiatric conditions, such as depression and anxiety. While many causes of low sexual desire are cited, only a few of these have ever been the object of empirical research.[8]

Sexual arousal disorders

Sexual arousal disorders were previously known as frigidity in women and impotence in men, though these have now been replaced with less judgmental terms. Impotence is now known as erectile dysfunction, and frigidity has been replaced with a number of terms describing specific problems that can be broken down into four categories as described by the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders: lack of desire, lack of arousal, pain during intercourse, and lack of orgasm.[9]

For both men and women, these conditions can manifest themselves as an aversion to and avoidance of sexual contact with a partner. In men, there may be partial or complete failure to attain or maintain an erection, or a lack of sexual excitement and pleasure in sexual activity.

There may be physiological origins to these disorders, such as decreased blood flow or lack of vaginal lubrication. Chronic disease can also contribute, as well as the nature of the relationship between the partners.

Additionally, the condition post-orgasm illness syndrome (POIS) may cause symptoms when aroused, including adrenergic-type presentation: rapid breathing, paresthesia, palpitations, headaches, aphasia, nausea, itchy eyes, fever, muscle pain and weakness, and fatigue.

From the onset of arousal, symptoms can persist for up to a week in patients.

The etiology of this condition is unknown; however, it is believed to be a pathology of either the immune system or autonomic nervous systems. It is defined as a rare disease by the NIH, but the prevalence is unknown. It is not thought to be psychiatric in nature, but it may present as anxiety relating to coital activities and thus may be incorrectly diagnosed as such. There is no known cure or treatment.[10]

Erectile dysfunction

Main page: Medicine:Erectile dysfunction

Erectile dysfunction (ED), or impotence, is a sexual dysfunction characterized by the inability to develop or maintain an erection of the penis. There are various underlying causes of erectile ED including: damage to anatomical structures, psychological causes, medical disease, as well as use of certain drugs. Many of these causes are medically treatable.

Psychological erectile dysfunction can often be helped by almost anything that the patient believes in; there is a very strong placebo effect. Physical damage can be more difficult to treat. One leading physical cause of ED is continual or severe damage taken to the nervi erigentes, which can prevent or delay erection. These nerves course beside the prostate arising from the sacral plexus and can be damaged in prostatic and colorectal surgeries.

Diseases are also common causes of erectile dysfunctional. Diseases such as cardiovascular disease, multiple sclerosis, kidney failure, vascular disease and spinal cord injury can cause erectile dysfunction.[11] Cardiovascular disease can decrease blood flow to tissues in the penis making it difficult to develop or maintain an erection.

Due to the shame and embarrassment felt by some sufferers of erectile dysfunction, the subject was taboo for a long time and is the focus of many urban legends. Folk remedies have long been advocated, with some being advertised widely since the 1930s. The introduction of perhaps the first pharmacologically effective remedy for impotence, sildenafil (trade name Viagra), in the 1990s caused a wave of public attention, propelled in part by the newsworthiness of stories about it and heavy advertising.

It is estimated that around 30 million men in the United States and 152 million men worldwide suffer from erectile dysfunction.[12][13] However, social stigma, low health literacy and social taboos lead to under reporting which makes an accurate prevalence rate hard to determine.

The Latin term impotentia coeundi describes simple inability to insert the penis into the vagina. It is now mostly replaced by more precise terms.

Erectile dysfunction from vascular disease is seen mainly amongst older individuals who have atherosclerosis. Vascular disease is common in individuals who have diabetes, peripheral vascular disease, hypertension, and those who smoke. Anytime blood flow to the penis is impaired, erectile dysfunction can occur.

Drugs are also a cause of erectile dysfunction. Individuals who take drugs that lower blood pressure, antipsychotics, antidepressants, sedatives, narcotics, antacids, or alcohol can have problems with sexual function and loss of libido.[14]

Hormone deficiency is a relatively rare cause of erectile dysfunction. In individuals with testicular failure, as in Klinefelter syndrome, or those who have had radiation therapy, chemotherapy or childhood exposure to mumps virus, the testes may fail and not produce testosterone. Other hormonal causes of erectile failure include brain tumors, hyperthyroidism, hypothyroidism, or disorders of the adrenal gland.[15]

Orgasm disorders

Anorgasmia

Main page: Medicine:Anorgasmia

Anorgasmia is classified as persistent delays or absence of orgasm following a normal sexual excitement phase in at least 75% of sexual encounters.[16]:368 The disorder can have physical, psychological, or pharmacological origins. SSRI antidepressants are a common pharmaceutical culprit, as they can delay orgasm or eliminate it entirely. A common physiological culprit of anorgasmia is menopause; one in three women report problems obtaining an orgasm during sexual stimulation following menopause.[17]

Premature ejaculation

Main page: Medicine:Premature ejaculation

Premature ejaculation is when ejaculation occurs before the partner achieves orgasm, or a mutually satisfactory length of time has passed during intercourse. There is no correct length of time for intercourse to last, but generally, premature ejaculation is thought to occur when ejaculation occurs in under two minutes from the time of the insertion of the penis.[18] For a diagnosis, the patient must have a chronic history of premature ejaculation, poor ejaculatory control, and the problem must cause feelings of dissatisfaction as well as distress for the patient, the partner or both.[19]

Historically attributed to psychological causes, new theories suggest that premature ejaculation may have an underlying neurobiological cause which may lead to rapid ejaculation.[20]

Post-orgasmic disorders

Post-orgasmic disorders cause symptoms shortly after orgasm or ejaculation. Post-coital tristesse (PCT) is a feeling of melancholy and anxiety after sexual intercourse that lasts for up to two hours. Sexual headaches occur in the skull and neck during sexual activity, including masturbation, arousal or orgasm.

In men, postorgasmic illness syndrome (POIS) causes severe muscle pain throughout the body and other symptoms immediately following ejaculation. These symptoms last for up to a week.[21][22][23] Some doctors speculate that the frequency of POIS "in the population may be greater than has been reported in the academic literature",[24] and that many POIS sufferers are undiagnosed.[25]

POIS may involve adrenergic symptoms: rapid breathing, paresthesia, palpitations, headaches, aphasia, nausea, itchy eyes, fever, muscle pain and weakness, and fatigue.

The etiology of this condition is unknown; however, it is believed to be a pathology of either the immune system or autonomic nervous systems. It is defined as a rare disease by the NIH, but the prevalence is unknown. It is not thought to be psychiatric in nature, but it may present as anxiety relating to coital activities and thus may be incorrectly diagnosed as such. There is no known cure or treatment.[10]

Dhat syndrome is another condition which occurs in men. It is a culture-bound syndrome which causes anxious and dysphoric mood after sex. It is distinct from the low-mood and concentration problems (acute aphasia) seen in POIS.

Sexual pain disorders

Sexual pain disorders in women include dyspareunia (painful intercourse) and vaginismus (an involuntary spasm of the muscles of the vaginal wall that interferes with intercourse).

Dyspareunia may be caused by insufficient lubrication (vaginal dryness) in women. Poor lubrication may result from insufficient excitement and stimulation, or from hormonal changes caused by menopause, pregnancy, or breastfeeding. Irritation from contraceptive creams and foams can also cause dryness, as can fear and anxiety about sex.

It is unclear exactly what causes vaginismus, but it is thought that past sexual trauma (such as rape or abuse) may play a role. Another female sexual pain disorder is called vulvodynia or vulvar vestibulitis. In this condition, women experience burning pain during sex which seems to be related to problems with the skin in the vulvar and vaginal areas. The cause is unknown.

In men, structural abnormalities of the penis like Peyronie's disease can make sexual intercourse difficult and/or painful. The disease is characterized by thick fibrous bands in the penis that lead to excessive curvature during erection.[26] It has an incidence estimated at 0.4–3% or more,[27] is most common in men 40–70,[27] and is of uncertain cause. Risk factors include genetics, minor trauma (including that occurring during cystoscopy or transurethral resection of the prostate), chronic systemic vascular diseases, smoking, and alcohol consumption.[28]

Priapism is a painful erection that occurs for several hours and occurs in the absence of sexual stimulation. This condition develops when blood gets trapped in the penis and is unable to drain. If the condition is not promptly treated, it can lead to severe scarring and permanent loss of erectile function. The disorder is most common in young men and children. Individuals with sickle-cell disease and those who use certain medications can often develop this disorder.[29]

Causes

There are many factors which may result in a person experiencing a sexual dysfunction. These may result from emotional or physical causes. Emotional factors include interpersonal or psychological problems, which can be the result of depression, sexual fears or guilt, past sexual trauma, and sexual disorders,[30] among others.

Sexual dysfunction is especially common among people who have anxiety disorders and the link is well established.[31][32][33][34] Ordinary anxiousness can cause erectile dysfunction in men without psychiatric problems, but clinically diagnosable disorders such as panic disorder commonly cause avoidance of intercourse and premature ejaculation.[35] Pain during intercourse is often a comorbidity of anxiety disorders among women.[36]

Physical factors that can lead to sexual dysfunctions include the use of drugs, such as alcohol, nicotine, narcotics, stimulants, antihypertensives, antihistamines, and some psychotherapeutic drugs.[37] For women, almost any physiological change that affects the reproductive system—premenstrual syndrome, pregnancy and the postpartum period, menopause—can have an adverse effect on libido.[37] Injuries to the back may also impact sexual activity, as can problems with an enlarged prostate gland, problems with blood supply, or nerve damage (as in sexual dysfunction after spinal cord injuries). Diseases such as diabetic neuropathy, multiple sclerosis, tumors, and, rarely, tertiary syphilis may also impact the activity, as could the failure of various organ systems (such as the heart and lungs), endocrine disorders (thyroid, pituitary, or adrenal gland problems), hormonal deficiencies (low testosterone, other androgens, or estrogen) and some birth defects.

In the context of heterosexual relationships, one of the main reasons for the decline in sexual activity among these couples is the male partner experiencing erectile dysfunction. This can be very distressing for the male partner, causing poor body image, and it can also be a major source of low desire for these men.[38] In aging women, it is natural for the vagina to narrow and become atrophied. If a woman has not been participating in sexual activity regularly (in particular, activities involving vaginal penetration), if she does decide to engage in penetrative intercourse, she will not be able to immediately accommodate a penis without risking pain or injury.[38] This can turn into a vicious cycle, often leading to female sexual dysfunction.[38]

According to Emily Wentzell, American culture has anti-aging sentiments that have caused sexual dysfunction to become "an illness that needs treatment" instead of viewing it as a natural part of the aging process. Not all cultures seek treatment; for example, a population of men living in Mexico often accept erectile dysfunction as a normal part of their maturing sexuality.[39]

Pelvic floor dysfunction

Pelvic floor dysfunction can be an underlying cause of sexual dysfunction in both women and men, and is treatable by pelvic floor physical therapy, a type of physical therapy designed to restore the health and function of the pelvic floor and surrounding areas.[40][41][42][43][44]

Female sexual dysfunction

Several theories have looked at female sexual dysfunction, from medical to psychological perspectives. Three social psychological theories include: the self-perception theory, the overjustification hypothesis, and the insufficient justification hypothesis:

  • Self-perception theory: people make attributions about their own attitudes, feelings, and behaviours by relying on their observations of external behaviours and the circumstances in which those behaviours occur
  • Overjustification hypothesis: when an external reward is given to a person for performing an intrinsically rewarding activity, the person's intrinsic interest will decrease
  • Insufficient justification: based on the classic cognitive dissonance theory (inconsistency between two cognitions or between a cognition and a behavior will create discomfort), this theory states that people will alter one of the cognitions or behaviours to restore consistency and reduce distress

The importance of how a woman perceives her behavior should not be underestimated. Many women perceived sex as a chore as opposed to a pleasurable experience, and they tend to consider themselves sexually inadequate, which in turn does not motivate them to engage in sexual activity.[38] Several factors influence a women's perception of her sexual life. These can include race, gender, ethnicity, educational background, socioeconomic status, sexual orientation, financial resources, culture, and religion.[38] Cultural differences are also present in how women view menopause and its impact on health, self-image, and sexuality. A study has found that African American women are the most optimistic about menopausal life; Caucasian women are the most anxious, Asian women are the most inhibited about their symptoms, and Hispanic women are the most stoic.[38]

About one-third of the women experienced sexual dysfunction, which may lead to these women's loss of confidence in their sexual lives. Since these women had sexual problems, their sexual lives with their partners can become a burden without pleasure, and eventually, they may completely lose interest in sexual activity. Some of the women found it hard to be aroused mentally; however, some had physical problems. Several factors can affect female dysfunction, such as situations in which women do not trust their sex partners, the environment where sex occurs being uncomfortable, or an inability to concentrate on the sexual activity due to a bad mood or burdens from work. Other factors include physical discomfort or difficulty in achieving arousal, which could be caused by aging or changes in the body's condition.[45]

Sexual assault has been associated with excessive menstrual bleeding, genital burning, and painful intercourse (whether attributable to disease, injury, or otherwise), medically unexplained dysmenorrhea, menstrual irregularity, and lack of sexual pleasure. Physically violent assaults and those committed by strangers were most strongly related to reproductive symptoms. Multiple assaults, assaults accomplished by persuasion, spouse assault, and completed intercourse were most strongly related to sexual symptoms. Assault was occasionally associated more strongly with reproductive symptoms among women with lower income or less education, possibly because of economic stress or differences in assault circumstances. Associations with unexplained menstrual irregularity were strongest among African American women; ethnic differences in reported circumstances of assault appeared to account for these differences. Assault was associated with sexual indifference only among Latinas.[46]

Menopause

The female sexual response system is complex and even today, not fully understood. The most prevalent of female sexual dysfunctions that have been linked to menopause include lack of desire and libido; these are predominantly associated with hormonal physiology. Specifically, the decline in serum estrogens causes these changes in sexual functioning. Androgen depletion may also play a role, but currently knowledge about this is less clear. The hormonal changes that take place during the menopausal transition have been suggested to affect women's sexual response through several mechanisms, some more conclusive than others.

Aging in women

Whether or not aging directly affects women's sexual functioning during menopause is another area of controversy. However, many studies, including Hayes and Dennerstein's critical review, have demonstrated that aging has a powerful impact on sexual function and dysfunction in women, specifically in the areas of desire, sexual interest, and frequency of orgasm.[3][38][47] In addition, Dennerstien and colleagues found that the primary predictor of sexual response throughout menopause is prior sexual functioning.[3] This means that it is important to understand how the physiological changes in men and women can affect their sexual desire.[38] Despite the seemingly negative impact that menopause can have on sexuality and sexual functioning, sexual confidence and well-being can improve with age and menopausal status.[3] Furthermore, the impact that a relationship status can have on quality of life is often underestimated.

Testosterone, along with its metabolite dihydrotestosterone, is extremely important to normal sexual functioning in men and women. Dihydrotestosterone is the most prevalent androgen in both men and women.[38] Testosterone levels in women at age 60 are, on average, about half of what they were before the women were 40. Although this decline is gradual for most women, those who have undergone bilateral oophorectomy experience a sudden drop in testosterone levels; this is because the ovaries produce 40% of the body's circulating testosterone.[38]

Sexual desire has been related to three separate components: drive, beliefs and values, and motivation.[38] Particularly in postmenopausal women, drive fades and is no longer the initial step in a woman's sexual response (if it ever was).[38]

Diagnosis

List of disorders

DSM

The fourth edition of the Diagnostic and Statistical Manual of Mental Disorders lists the following sexual dysfunctions:

Additional DSM sexual disorders that are not sexual dysfunctions include:

  • Paraphilias
  • PTSD due to genital mutilation or childhood sexual abuse

Other sexual problems

  • Sexual dissatisfaction (non-specific)
  • Lack of sexual desire
  • Anorgasmia
  • Impotence
  • Sexually transmitted diseases
  • Delay or absence of ejaculation, despite adequate stimulation
  • Inability to control timing of ejaculation
  • Inability to relax vaginal muscles enough to allow intercourse
  • Inadequate vaginal lubrication preceding and during intercourse
  • Burning pain on the vulva or in the vagina with contact to those areas
  • Unhappiness or confusion related to sexual orientation
  • Transsexual and transgender people may have sexual problems before or after surgery.
  • Persistent sexual arousal syndrome
  • Sexual addiction
  • Hypersexuality
  • All forms of female genital cutting
  • Post-orgasmic diseases, such as Dhat syndrome, post-coital tristesse (PCT), postorgasmic illness syndrome (POIS), and sexual headache.

Treatment

Males

Several decades ago, the medical community believed most sexual dysfunction cases were related to psychological issues. Although this may be true for a portion of men, the vast majority of cases have now been identified as having a physical cause or correlation.[48] If the sexual dysfunction is deemed to have a psychological component or cause, psychotherapy can help. Situational anxiety arises from an earlier bad incident or lack of experience. This anxiety often leads to development of fear towards sexual activity and avoidance. In return evading leads to a cycle of increased anxiety and desensitization of the penis. In some cases, erectile dysfunction may be due to marital disharmony. Marriage counseling sessions are recommended in this situation.

Lifestyle changes such as discontinuing tobacco smoking or substance use can also help in some types of erectile dysfunction.[49] Several oral medications like Viagra, Cialis and Levitra have become available to help people with erectile dysfunction and have become first line therapy. These medications provide an easy, safe, and effective treatment solution for approximately 60% of men. In the rest, the medications may not work because of wrong diagnosis or chronic history.

Another type of medication that is effective in roughly 85% of men is called intracavernous pharmacotherapy and involves injecting a vasodilator drug directly into the penis in order to stimulate an erection.[50] This method has an increased risk of priapism if used in conjunction with other treatments, and localized pain.[19]

When conservative therapies fail, are an unsatisfactory treatment option, or are contraindicated for use, the insertion of a penile implant may be selected by the patient. Technological advances have made the insertion of a penile implant a safe option for the treatment of erectile dysfunction which provides the highest patient and partner satisfaction rates of all available ED treatment options.[51]

Pelvic floor physical therapy has been shown to be a valid treatment for men with sexual problems and pelvic pain.[52]

The 2020 guidelines from the American College of Physicians support the discussion of testosterone treatment in adult men with age-related low levels of testosterone who have sexual dysfunction. They recommend yearly evaluation regarding possible improvement and, if none, to discontinue testosterone; intramuscular treatments should be considered rather than transdermal treatments due to costs and since the effectiveness and harm of either method is similar. Testosterone treatment for reasons other than possible improvement of sexual dysfunction may not be recommended.[53][54]

Females

In 2015, flibanserin was approved in the US to treat decreased sexual desire in women. While it's effective for some women, it has been criticized for its limited efficacy, and many warnings and contraindications that limit its use.[55] Women experiencing pain with intercourse are often prescribed pain relievers or desensitizing agents; others can be prescribed vaginal lubricants. Many women with sexual dysfunction are also referred to a counselor or sex therapist.[56]

Menopause

Estrogens are responsible for the maintenance of collagen, elastic fibers, and vasculature of the urogenital tract, all of which are important in maintaining vaginal structure and functional integrity; they are also important for maintaining vaginal pH and moisture levels, both of which aid in keeping the tissues lubricated and protected.[3] Prolonged estrogen deficiency leads to atrophy, fibrosis, and reduced blood flow to the urogenital tract, which is what causes menopausal symptoms such as vaginal dryness and pain related to sexual activity and/or intercourse.[3] It has been consistently demonstrated that women with lower sexual functioning have lower estradiol levels.[3] Women experiencing vaginal dryness who cannot use commercial lubricants may be able to use coconut oil as an alternative.

Androgen therapy for hypoactive sexual desire disorder (HSDD) has a small benefit but its safety is not known.[57] It is not approved as a treatment in the United States.[57] If used it is more common among women who have had an oophorectomy or who are in a postmenopausal state. However, like most treatments, this is also controversial. One study found that after a 24-week trial, those women taking androgens had higher scores of sexual desire compared to a placebo group.[3] As with all pharmacological drugs, there are side effects in using androgens, which include hirsutism, acne, ploycythaemia, increased high-density lipoproteins, cardiovascular risks, and endometrial hyperplasia is a possibility in women without hysterectomy.[3] Alternative treatments include topical estrogen creams and gels can be applied to the vulva or vagina area to treat vaginal dryness and atrophy.[3]

Research

In modern times, the genuine clinical study of sexual problems is usually dated back no further than 1970 when Masters and Johnson's Human Sexual Inadequacy was published. It was the result of over a decade of work at the Reproductive Biology Research Foundation in St. Louis, involving 790 cases. The work grew from Masters and Johnson's earlier Human Sexual Response (1966).

Prior to Masters and Johnson, the clinical approach to sexual problems was largely derived from the thinking of Freud. It was held to be psychopathology and approached with a certain pessimism regarding the chance of help or improvement. Sexual problems were merely symptoms of a deeper malaise, and the diagnostic approach was from the psychopathological viewpoint. There was little distinction between difficulties in function and variations nor between perversion and problems. Despite work by psychotherapists such as Balint sexual difficulties were crudely split into frigidity or impotence, terms which too soon acquired negative connotations in popular culture.

The achievement of Human Sexual Inadequacy was to move thinking from psychopathology to learning, only if a problem did not respond to educative treatment would psychopathological problems be considered. Also, treatment was directed at couples, whereas before partners would be seen individually. Masters and Johnson saw that sex was a joint act. They believed that sexual communication was the key issue to sexual problems not the specifics of an individual problem. They also proposed co-therapy, a matching pair of therapists to the clients, arguing that a lone male therapist could not fully comprehend female difficulties.

The basic Masters and Johnson treatment program was an intensive two-week program to develop efficient sexual communication. Couple-based and therapist led the program began with discussion and then sensate focus between the couple to develop shared experiences. From the experiences specific difficulties could be determined and approached with a specific therapy. In a limited number of male only cases (41) Masters and Johnson had developed the use of a female surrogate, an approach they soon abandoned over the ethical, legal, and other problems it raised.

In defining the range of sexual problems Masters and Johnson defined a boundary between dysfunction and deviations. Dysfunctions were transitory and experienced by most people, dysfunctions bounded male primary or secondary impotence, premature ejaculation, ejaculatory incompetence; female primary orgasmic dysfunction and situational orgasmic dysfunction; pain during intercourse (dyspareunia) and vaginismus. According to Masters and Johnson sexual arousal and climax are a normal physiological process of every functionally intact adult, but despite being autonomic it can be inhibited. Masters and Johnson treatment program for dysfunction was 81.1% successful.

Despite the work of Masters and Johnson the field in the US was quickly overrun by enthusiastic rather than systematic approaches, blurring the space between 'enrichment' and therapy. Although it has been argued that the impact of the work was such that it would be impossible to repeat such a clean experiment.

See also

References

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