There are no laboratory tests or unique physical findings to verify the diagnosis of PMS. The three key features are:

- The woman's chief complaint is one or more of the emotional symptoms associated with PMS (most typically irritability, tension, or unhappiness). The woman does not have PMS if she only has physical symptoms, such as cramps or bloating.

- Symptoms appear predictably during the luteal (premenstrual) phase, reduce or disappear predictably shortly before or during menstruation, and remain absent during the follicular (preovulatory) phase.

- The symptoms must be severe enough to interfere with the woman's everyday life.

Mild PMS is common, and more severe symptoms would qualify as PMDD. PMS is not listed in the DSM-IV, unlike PMDD. To establish a pattern and determine if it is PMDD, a woman's physician may ask her to keep a prospective record of her symptoms on a calendar for at least two menstrual cycles. This will help to establish if the symptoms are, indeed, limited to the premenstrual time, predictably recurring, and disruptive to normal functioning. A number of standardized instruments have been developed to describe PMS, including the "Calendar of Premenstrual syndrome Experiences (COPE)", the "Prospective Record of the Impact and Severity of Menstruation (PRISM)", and the "Visual Analogue Scales (VAS)".

Other conditions that may better explain symptoms must be excluded. A number of medical conditions are subject to exacerbation at menstruation, a process called "menstrual magnification." These conditions may lead the woman to believe that she has PMS, when the underlying disorder may be some other problem, such as anemia, hypothyroidism, eating disorders and substance abuse. A key feature is that these conditions may also be present outside of the luteal phase. Conditions that can be magnified perimenstrually include depression or other affective disorders, migraine, seizure disorders, fatigue, irritable bowel syndrome, asthma, and allergies. Problems with other aspects of the female reproductive system must be excluded, including dysmenorrhea (pain during the menstrual period, rather than before it), endometriosis, perimenopause, and adverse effects produced by oral contraceptive pills.

The National Institute of Mental Health research definition compares the intensity of symptoms from cycle days 5 to 10 to the six-day interval before the onset of the menstrual period. To qualify as PMS, symptom intensity must increase at least 30% in the six days before menstruation. Additionally, this pattern must be documented for at least two consecutive cycles.

PMS is generally a stable diagnosis, with susceptible women experiencing the same symptoms at the same intensity near the end of each cycle for years. Treatment for specific symptoms is usually effective.

Even without treatment, symptoms tend to decrease in perimenopausal women. However, women who experience PMS or PMDD are more likely to have significant symptoms associated with menopause, such as hot flashes.

Authoritative diagnostic criteria for PMDD are provided by a number of expert medical guides, notably the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5). The "Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)," established seven criteria (A through G) for the diagnosis of PMDD.

Diagnostic Criteria:

Criterion A is that in most menstrual cycles during the past year, at least 5 of the following 11 symptoms (including at least 1 of the first 4 listed) must be present in the final week before the onset of menses, start to improve within a few days after the onset of menses, and become minimal or absent in the week postmenses.

1. Marked lability (e.g., mood swings)

2. Marked irritability or anger

3. Markedly depressed mood

4. Marked anxiety and tension

5. Decreased interest in usual activities

6. Difficulty in concentration

7. Lethargy and marked lack of energy

8. Marked change in appetite (e.g., overeating or specific food cravings)

9. Hypersomnia or insomnia

10. Feeling overwhelmed or out of control

11. Physical symptoms (e.g., breast tenderness or swelling, joint or muscle pain, a sensation of ‘bloating’ and weight gain)

Criterion B one (or more) of the following symptoms must be present:

1. Marked affective lability (e.g., mood swings; feeling suddenly sad or tearful, or increased sensitivity to rejection).

2. Marked irritability or anger or increased interpersonal conflicts.

3. Marked depressed mood, feelings of hopelessness, or self-deprecating thoughts.

4. Marked anxiety, tension, and/or feelings of being keyed up or on edge.

Criterion C one (or more) of the following symptoms must be present additionally, to reach a total of "five" symptoms when combined with symptoms from Criterion B above.

1. Decreased interest in usual activities (e.g., work, school, friends, hobbies).

2. Subjective difficulty in concentration.

3. Lethargy, easy fatigability, or marked lack of energy.

4. Marked change in appetite; overeating; or specific food cravings.

5. Hypersomnia or insomnia.

6. A sense of being overwhelmed or out of control.

7. Physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of "bloating," or weight gain.

Note: The symptoms in Criteria A-C must have been met for most menstrual cycles that occurred in the preceding year.

Criterion D The symptoms are associated with clinically significant distress or interference with work, school, usual social activities, or relationships with others (e.g., avoidance of social activities; decreased productivity and efficiency at work, school, or home).

Criterion E The disturbance is not merely an exacerbation of the symptoms of another disorder, such as major depressive disorder, panic disorder, persistent depressive disorder (dysthymia), or a personality disorder (although it may co-occur with any of these disorders).

Criterion F Criterion A should be confirmed by prospective daily ratings during at least two symptomatic cycles. (Note: The diagnosis may be made provisionally prior to this confirmation.)

Criterion G The symptoms are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication, other treatment) or another medical condition (e.g., hyperthyroidism).

According to the DSM-5, a diagnosis of PMDD requires the presence of at least five of these symptoms with one of the symptoms being number 1-4 (marked lability, irritability, depressed mood, anxiety and tension). These symptoms should occur during the week before menses and remit after initiation of menses. In order to meet criteria for the diagnosis, the symptoms should be charted prospectively for two consecutive ovulation cycles in order to confirm temporal and cyclical nature of symptoms. The symptoms should also be severe enough to affect normal work, school, or social activities or relationships with others.

Other organizations that have published diagnostic criteria for PMDD include the American College of Obstetricians and Gynecologists, the Royal College of Obstetricians and Gynecologists, and the International Society for the Study of Premenstrual Disorders (ISPMD). The ISPMD was a consensus group established by an international multidisciplinary group of experts. The group's diagnostic criteria for PMDD focuses on the cyclic nature of the symptom occurring during the luteal phase of the menstrual cycle, symptoms being absent after menstruation and before ovulation and causing significant impairment. The ISPMD diagnostic criteria for PMDD do not specify symptom characteristics or number of symptoms.

Diagnostic criteria for PMDD are also provided by the 2016 World Health Organization's International Classification of Diseases (ICD-10-CM):

Premenstrual tension syndrome

A more severe and disabling form of premenstrual syndrome in which mood symptoms are the primary characteristic.

A term used to describe the psychological aspects of premenstrual syndrome, such as the "indescribable tension", depression, hostility, and increased seizure activity in people with seizure disorder.

Applicable To

Premenstrual dysphoric disorder ...

Thus today many well-recognized health organizations in many parts of the world provide guides for the diagnosis of PMDD. As a historical footnote, early drafts of the ICD failed to recognize PMDD as a separate condition. In 2003, before the current ICD 10 guidelines, the Committee for Proprietary Medicinal Products required the manufacturer of Prozac (fluoxetine) to remove PMDD from the list of indications for fluoxetine sold in Europe. Reflecting an earlier approach by the ICD, the committee found in 2003 that PMDD was not a well-established disease entity across Europe, and noted "considerable concern that [people] with less severe pre-menstrual symptoms might erroneously receive a diagnosis of PMDD resulting in widespread inappropriate short and long-term use of fluoxetine."

In Australia, PMDD is recognized by the Therapeutic Goods Administration. However, SSRIs are not reimbursed for PMDD under the Pharmaceutical Benefits Scheme.

Medication may be used for people with severe and debilitating symptoms. Selective serotonin reuptake inhibitors (SSRIs) are the first-line medication. The U.S. Food and Drug Administration (FDA) has approved four SSRIs for the treatment of PMDD: Fluoxetine (available as generic or as Prozac or Sarafem), sertraline (Zoloft), paroxetine (Paxil), and escitalopram oxalate (Lexapro). Unlike treatments for depressive disorders, SSRIs do not need to be taken daily but instead can be taken only in the luteal phase or during PMDD symptoms. This is because those who respond to SSRIs usually experience symptoms relief within 1–2 days. Studies in rats suggest this rapid response to SSRIs is due to the elevation of the neuroactive progesterone metabolite allopregnanolone in the brain, rather than serotonin. Luteal phase dosing can be started 14 days before menses and subsequently discontinued after start of menstrual flow. People taking SSRIs to ease PMDD generally report >50% alleviation in symptoms, which was significant improvement compared to placebo.

Although less studied, SNRIs have also shown benefit in PMDD. In a randomized, controlled clinical trial of people with PMDD, 60% of the people taking venlafaxine improved versus 35% on placebo. Improvement was noticed during the first treatment cycle with 80% symptom reduction.

Another FDA approved treatment for PMDD is the oral contraceptive with ethinylestradiol and drospirenone, a novel progestin. It has been shown that hormonal birth control containing drospirenone and low levels of estrogen helps relieve severe PMDD symptoms, for at least the first three months it is used. The idea behind using oral contraceptives is to suppress ovulation by controlling sex hormone fluctuations during the luteal phase.

Cyclical breast pain (cyclical mastalgia) is often associated with fibrocystic breast changes or duct ectasia and thought to be caused by changes of prolactin response to thyrotropin. Some degree of cyclical breast tenderness is normal in the menstrual cycle, and is usually associated with menstruation and/or premenstrual syndrome (PMS).

Noncyclical breast pain has various causes and is harder to diagnose. Noncyclical pain has frequently its root cause outside the breast. Some degree of non-cyclical breast tenderness can normally be present due to hormonal changes in puberty (both in girls and boys), in menopause and during pregnancy. After pregnancy, breast pain can be caused by breastfeeding. Other causes of non-cyclical breast pain include alcoholism with liver damage (likely due to abnormal steroid metabolism), mastitis and medications such as digitalis, methyldopa (an antihypertensive), spironolactone, certain diuretics, oxymetholone (an anabolic steroid), and chlorpromazine (a typical antipsychotic). Also, shingles can cause a painful blistering rash on the skin of the breasts.

Ruling out the other possible causes of the pain is one way to differentiate the source of the pain. Breast pain can be due to:

- angina pectoris

- anxiety and depression

- bra

- blocked milk duct

- breastfeeding

- chest wall muscle pain

- consensual, rough sex

- costal chondritis (sore ribs)

- cutaneous candida infection

- duct ectasia (often with nipple discharge)

- engorgement

- fibroadenoma

- fibrocystic breast changes

- fibromyalgia

- gastroesophageal reflux disease

- herpes infection

- hormone replacement therapy

- mastalgia

- mastitis or breast infection

- menopause

- menstruation and Premenstrual syndrome

- perimenopause

- neuralgia

- pregnancy

- physical abuse

- pituitary tumor (often with nipple discharge)

- puberty in both girls and boys

- sexual abuse

- shingles

- sore nipples and cracked nipples

- surgery or biopsy

- trauma (including falls)

Medications can be associated with breast pain and include:

- Oxymetholone

- Chlorpromazine

- Water pills (diuretics)

- Digitalis preparations

- Methyldopa

- Spironolactone

Diagnostic testing can be useful. Typical tests used are mammogram, excisional biopsy for solid lumps, fine-needle aspiration and biopsy, pregnancy test, ultrasonography, and magnetic resonance imaging (MRI).

Wilson's (temperature) syndrome, also called Wilson's thyroid syndrome or WTS, is an alternative medicine concept which is not recognized as a medical condition by evidence-based medicine. Its supporters describe Wilson's syndrome as a mix of various common and non-specific symptoms which they attribute to low body temperature and impaired conversion of thyroxine (T4) to triiodothyronine (T3), despite normal thyroid function tests. E. Denis Wilson, a physician who named the syndrome after himself, advocates treating these symptoms with sustained-release triiodothyronine.

The American Thyroid Association (ATA) describes Wilson's syndrome as at odds with established knowledge of thyroid function. The ATA described the diagnostic criteria for Wilson's syndrome as imprecise and non-specific, and found a lack of any scientific evidence supporting Wilson's claims. The ATA further raised concern that the proposed treatments were potentially harmful. Florida State Medical Board members described Wilson's syndrome as a "phony syndrome" and a scam during disciplinary action against Wilson.

Pregnant women who are positive for Hashimoto's thyroiditis may have decreased thyroid function or the gland may fail entirely. If a woman is TPOAb-positive, clinicians can inform her of the risks for themselves and their infants if they go untreated. "Thyroid peroxidase antibodies (TPOAb) are detected in 10% of pregnant women," which presents risks to those pregnancies. Women who have low thyroid function that has not been stabilized are at greater risk of having an infant with: low birth weight, neonatal respiratory distress, hydrocephalus, hypospadias, miscarriage, and preterm delivery. The embryo transplantion rate and successful pregnancy outcomes are improved when Hashimoto's is treated. Recommendations are to only treat pregnant women who are TPOAb-positive throughout the entirety of their pregnancies and to screen all pregnant women for thyroid levels. Close cooperation between the endocrinologist and obstetrician benefits the woman and the infant. The Endocrine Society recommends screening in pregnant women who are considered high-risk for thyroid autoimmune disease.

Thyroid peroxides antibodies testing is recommended for women who have ever been pregnant regardless of pregnancy outcome. "...[P]revious pregnancy plays a major role in development of autoimmune overt hypothyroidism in premenopausal women, and the number of previous pregnancies should be taken into account when evaluating the risk of hypothyroidism in a young women ["sic"]."

1. Clinical Genetics and Genetic Testing

Genetic testing is necessary to confirm the diagnosis of PMS. A prototypical terminal deletion of 22q13 can be uncovered by karyotype analysis, but many terminal and interstitial deletions are too small to detect with this method. Chromosomal microarray should be ordered in children with suspected developmental delays or ASD. Most cases will be identified by microarray; however, small variations in genes might be missed. The falling cost for whole exome sequencing may replace DNA microarray technology for candidate gene evaluation. Biological parents should be tested with fluorescence "in situ" hybridization (FISH) to rule out balanced translocations or inversions. Balanced translocation in a parent increases the risk for recurrence and heritability within families (figure 3).

Clinical genetic evaluations and dysmorphology exams should be done to evaluate growth, pubertal development, dysmorphic features (table 1) and screen for organ defects (table 2)

2. Cognitive and Behavioral Assessment

All patients should undergo comprehensive developmental, cognitive and behavioral assessments by clinicians with experience in developmental disorders. Cognitive evaluation should be tailored for individuals with significant language and developmental delays. All patients should be referred for specialized speech/language, occupational and physical therapy evaluations.

3. Neurological Management

Individuals with PMS should be followed by a pediatric neurologist regularly to monitor motor development, coordination and gait, as well as conditions that might be associated with hypotonia. Head circumference should be performed routinely up until 36 months. Given the high rate of seizure disorders (up to 41% of patients) reported in the literature in patients with PMS and its overall negative impact on development, an overnight video EEG should be considered early to rule out seizure activity. In addition, a baseline structural brain MRI should be considered to rule out the presence of structural abnormalities.

4. Nephrology

All patients should have a baseline renal and bladder ultrasonography and a voiding cystourethrogram should be considered to rule out structural and functional abnormalities. Renal abnormalities are reported in up to 38% of patients with PMS. Vesicouretral reflux, hydronephrosis, renal agenesis, dysplasic kidney, polycystic kidney and recurrent urinary tract infections have all been reported in patients with PMS.

5. Cardiology

Congenital heart defects (CHD) are reported in samples of children with PMS with varying frequency (up to 25%)(29,36). The most common CHD include tricuspid valve regurgitation, atrial septal defects and patent ductus arteriousus. Cardiac evaluation, including echocardiography and electrocardiogram, should be considered.

6. Gastroenterology

Gastrointestinal symptoms are common in individuals with PMS. Gastroesophageal reflux, constipation, diarrhea and cyclic vomiting are frequently described.

Table 3: Clinical Assessment Recommendations in Phelan McDermid Syndrome.

Diagnosis is usually made by detecting elevated levels of anti-thyroid peroxidase antibodies (TPOAb) in the serum, but seronegative (without circulating autoantibodies) thyroiditis is also possible.

Given the relatively non-specific symptoms of initial hypothyroidism, Hashimoto's thyroiditis is often misdiagnosed as depression, cyclothymia, PMS, chronic fatigue syndrome, fibromyalgia and, less frequently, as erectile dysfunction or an anxiety disorder. On gross examination, there is often presentation of a hard goiter that is not painful to the touch; other symptoms seen with hypothyroidism, such as periorbital myxedema, depend on the current state of progression of the response, especially given the usually gradual development of clinically relevant hypothyroidism. Testing for thyroid-stimulating hormone (TSH), free T3, free T4, and the anti-thyroglobulin antibodies (anti-Tg), anti-thyroid peroxidase antibodies (anti-TPO, or TPOAb) and anti-microsomal antibodies can help obtain an accurate diagnosis. Earlier assessment of the person may present with elevated levels of thyroglobulin owing to transient thyrotoxicosis, as inflammation within the thyroid causes damage to the integrity of thyroid follicle storage of thyroglobulin; TSH secretion from the anterior pituitary increases in response to a decrease in negative feedback inhibition secondary to decreased serum thyroid hormones. Typically T4 is the preferred thyroid hormone test for hypothyroidism. This exposure of the body to substantial amounts of previously isolated thyroid enzymes is thought to contribute to the exacerbation of tolerance breakdown, giving rise to the more pronounced symptoms seen later in the disease. Lymphocytic infiltration of the thyrocyte-associated tissues often leads to the histologically significant finding of germinal center development within the thyroid gland.

Hashimoto's when presenting as mania is known as Prasad's syndrome after Ashok Prasad, the psychiatrist who first described it.

The term "Wilson’s syndrome" was coined in 1990 by E. Denis Wilson, a physician practicing in Longwood, Florida. Wilson said that the syndrome's manifestations included fatigue, headaches, PMS, hair loss, irritability, fluid retention, depression, decreased memory, low sex drive, unhealthy nails, easy weight gain, and about 60 other symptoms. Wilson wrote that the syndrome can manifest itself as "virtually every symptom known to man." He also says that it is "the most common of all chronic ailments and probably takes a greater toll on society than any other medical condition."

Wilson says that low thyroid symptoms and low temperatures in the presence of normal thyroid function tests are not due to hypothyroidism, and might be reversed with a few months of treatment. To distinguish this condition from hypothyroidism, he named it Wilson's (temperature) syndrome. He states that it is "especially brought on by stress" and can persist after the stress has passed. He says that the main diagnostic sign is a body temperature that averages below (oral), and that the diagnosis is confirmed if the patient responds to treatment with a "special thyroid hormone treatment". He says that certain herbs can also help support normal body temperatures.

The true prevalence of PMS has not been determined. More than 1200 people have been identified worldwide according the Phelan-McDermid Syndrome Foundation. However, it is believed to be underdiagnosed due to inadequate genetic testing and lack of specific clinical features. It is known to occur with equal frequency in males and females. Studies using chromosomal microarray for diagnosis indicate that at least 0.5% of cases of ASD can be explained by mutations or deletions in the "SHANK3" gene. In addition when ASD is associated with ID, "SHANK3" mutations or deletions have been found in up to 2% of individuals.