A condition characterized by nervousness, irritability, emotional instability, anxiety, depression, and possibly headaches, edema, and mastalgia, occurring during the 7 to 10 days before and usually disappearing a few hours after onset of menses.

Etiology
Premenstrual syndrome (PMS) appears to be related to fluctuations in estrogen and progesterone. Estrogen and progesterone may cause transitory fluid retention, which seems to explain some PMS symptoms. Recent data suggest that women with PMS metabolize progesterone differently, producing less allopregnanolone (a neurosteroid that enhances GABAA receptor function in the brain and that has anxiolytic effects). Production of pregnenolone, which has an opposite effect in the brain, may be increased.

Pathogenesis

The etiology of the symptom complex of PMS is not known, although several theories have been proposed, including estrogen-progesterone imbalance, excess aldosterone, hypoglycemia, hyperprolactinemia, and psychogenic factors. A hormonal imbalance previously was thought to be related to the clinical manifestations of PMS/PMDD, but in the most recent consensus, physiologic ovarian function is believed to be the trigger. This is supported by the efficacy of ovarian cyclicity suppression, either medically or surgically, in eliminating premenstrual complaints.

Additional Reading Premenstrual syndrome (PMS) -Disorders of the Ovary and Female Reproductive Tract Premenstrual Syndrome (Premenstrual Tension) Premenstrual Syndrome (Premenstrual Tension) -1 Premenstrual symptoms getting on your nerves? Hormone Fluctuations May be Responsible for Many Mood Disturbances in Women First significant genetic finding in severe PMS, or PMDD Women with severe PMS perceive their sleep quality to be poor Low Doses of Anti-Depressant May Help PMS Adolescent Dysmenorrhea Prevalence

Further research has shown that serotonin (5-hydroxytryptamine [5-HT]), a neurotransmitter, is important in the pathogenesis of PMS/PMDD. Both estrogen and progesterone have been shown to influence the activity of serotonin centrally. Many of the symptoms of other mood disorders resembling the features of PMS/PMDD have been associated with serotonergic dysfunction.

Diagnosis
No objective screening or diagnostic tests for PMS and PMDD are available; thus special attention must be paid to the patient’s medical history. Certain medical conditions (eg, thyroid disease and anemia) with symptoms that can mimic those of PMS/PMDD must be ruled out.

The patient is instructed to chart her symptoms for at least 2 symptomatic cycles. The classic criteria for PMS require that the patient have symptoms in the luteal phase and a symptom-free period of at least 7 days in the first half of the cycle for a minimum of 2 consecutive symptomatic cycles. To meet the criteria for PMDD, in addition to the criteria for PMS, she must have a chief complaint of at least 1 of the following: irritability, tension, dysphoria, or mood lability; and 5 of 11 of the following: depressed mood, anxiety, affective lability, irritability, decreased interest in daily activities, concentration difficulties, lack of energy, change in appetite or food cravings, sleep disturbances, feeling overwhelmed, or physical symptoms (eg, breast tenderness, bloating).

Causes
The exact cause of premenstrual syndrome (PMS) is not fully understood, but there are a number of possible factors that may contribute to the symptoms. These are detailed below.

Hormonal changes
During your menstrual cycle, levels of hormones, such as oestrogen and progesterone, rise and fall. Hormonal changes are thought to be the biggest contributing factor to many of the symptoms of PMS. The fact that PMS improves during pregnancy, and after the menopause, when hormone levels are stable, supports this theory.

Chemical changes
Like your hormone levels, certain chemicals in your brain, such as serotonin, fluctuate during your menstrual cycle. Serotonin is known to help regulate your mood and make you feel happier, and so it is possible that women with low levels of serotonin are particularly sensitive to the symptoms of PMS. Low levels of serotonin may also contribute to symptoms such as tiredness, food cravings, and insomnia (difficulty sleeping).

Stress
You may find that your symptoms of PMS become worse the more stressed you are. While it is not a direct cause, being stressed can aggravate the symptoms of PMS.

Diet
Eating too much of some foods, and too little of others, may also contribute to the symptoms of PMS. For example, too much salty food may add to fluid retention, and make you feel bloated, and alcohol and caffeinated drinks can disrupt your mood and energy levels. Low levels of vitamins and minerals may also make your symptoms of PMS worse.

Symptoms and Signs
The type and intensity of symptoms vary from woman to woman and from cycle to cycle. In many, symptoms are significant but brief and not disabling; in others, normal functioning is disturbed. Symptoms last a few hours to >= 10 days, usually ceasing when menses begins; however, in perimenopausal women, symptoms may persist through and after menses. When menses begins, some women develop dysmenorrhea. Significant dysmenorrhea is more common among teenagers and tends to diminish with age.

The most common complaints are mood alteration and psychologic effects-irritability, nervousness, lack of control, agitation, anger, insomnia, difficulty in concentrating, lethargy, depression, and severe fatigue. Fluid retention causes edema, transient weight gain, oliguria, and breast fullness and pain. Neurologic and vascular symptoms include headache, vertigo, syncope, paresthesias of the extremities, easy bruising, and cardiac palpitation. Epilepsy may be aggravated. GI symptoms include constipation, nausea, vomiting, and changes in appetite. Pelvic heaviness or pressure and backache may occur. Acne, neurodermatitis, and aggravation of other skin disorders may also occur. Respiratory problems (eg, allergies, infection) and eye complaints (eg, visual disturbance, conjunctivitis) may worsen.

The following are the most common symptoms of premenstrual syndrome. However, each individual may experience symptoms differently.
Symptoms may include:

psychological symptoms

 
• irritability  
• nervousness  
• lack of control  
• agitation  
• anger  
• insomnia  
• difficulty in concentrating  
• lethargy  
• depression  
• severe fatigue  
• anxiety  
• confusion  
• forgetfulness  
• decreased self-image  
• paranoia  
• emotional hypersensitivity  
• crying spells  
• moodiness  
• sleep disturbances

behavioral symptoms

 
• fatigue  
• dizziness  
• changes in sexual interest  
• food cravings or overeating

fluid retention

 
• edema (swelling of the ankles, hands, and feet)  
• periodic weight gain  
• oliguria (diminished urine formation)  
• breast fullness and pain  
• breast tenderness and swelling

respiratory problems

 
• allergies  
• infections

eye complaints

 
• visual disturbances  
• conjunctivitis

gastrointestinal symptoms

 
• abdominal cramps  
• abdominal pain and bloating  
• bloating  
• constipation  
• nausea  
• vomiting  
• pelvic heaviness or pressure  
• backache

skin problems

 
• acne  
• neurodermatitis (skin inflammation with itching)  
• aggravation of other skin disorders, including cold sores

neurologic and vascular symptoms

 
• headache  
• vertigo  
• syncope (fainting)  
• numbness, prickling, tingling, or heightened sensitivity of arms and/or legs  
• easy bruising  
• heart palpitations  
• muscle spasms

other

 
• decreased coordination  
• painful menstruation  
• diminished libido (sex drive)  
• appetite changes  
• food cravings  
• hot flashes

Risk Factors

• High caffeine intake
• Stress may precipitate condition.
• Increasing age
• History of depression
• Tobacco use
• Family history

Treatment
Treatment involves relief of symptoms. Fluid retention may be relieved by reducing sodium intake and using a diuretic (eg, hydrochlorothiazide 25 to 50 mg/day po), starting just before symptoms are expected. Diuretics promote sodium and water excretion but do not relieve all symptoms and may have no effect. Counseling may help the woman and her partner cope with PMS, and the woman’s activities can be modified to reduce stress. For some women, hormonal manipulation is effective. Regimens include oral contraceptives; progesterone by vaginal suppository (200 to 400 mg/day) or by injection (5 to 10 mg IM in oil) for 10 to 12 days premenstrually; a long-acting progestin (eg, medroxyprogesterone acetate 200 mg IM q 2 to 3 mo); or a gonadotropin-releasing hormone agonist (eg, leuprolide 3.75 mg IM or goserelin 3.6 mg IM monthly) with low-dose estrogen-progestin “add-back” therapy to eliminate cyclic changes. Tranquilizers (eg, a benzodiazepine) may be used for irritability, nervousness, and lack of control, especially if patients cannot alter their stressful environments. Changing the diet (eg, increasing protein, decreasing sugars) and supplementing with vitamin B complex (especially pyridoxine, sometimes with magnesium) may help. Spironolactone, bromocriptine, and monoamine oxidase inhibitors are not beneficial. Selective serotonin reuptake inhibitors (eg, fluoxetine 20 mg po daily, sertraline 50 mg po daily) are the most effective drugs in the management of psychologic and physical PMS symptoms.

Johnson S: Premenstrual syndrome, premenstrual dysphoric disorder, and beyond: A clinical primer for practitioners. Obstet Gynecol 2004;104:845.

References
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