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by: William Mann MD Univ of North Dakota School of Medicine


Case History

An unemployed nulliparous 19-year-old woman was arrested for stabbing her boyfriend while intoxicated. Menarche was at 13 years, and she had been well with no behavioral problem until l5, when she began to exhibit paroxysmal aberrant behavior including: slashing her wrists, shoplifting, arson, promiscuity, alcohol intoxication, expulsion from school for assaulting teachers, and mutilation of her hands and feet with cuts and cigarette burns. In prison, prior to her next four menstrual periods, she assaulted a guard, tried to hang herself, cut her wrists, and attempted to escape. During the rest of her cycle, she was cooperative, rational, and penitent. All past episodes of aberrant behavior which could be accurately dated, occurred on a cycle length of 29+- 2.5 days.

Initially in prison she was treated with Chlorpromazine 100mg bid and fluphenazine injections 20 mg every 10 days. She stated that she felt a little calmer, but depressed, with continued cyclic suicidal impulses and a wish to "escape from life". On several occasions during the premenstruum she requested that she be locked up alone and expressed fear that she was going to lose control.

She was started on medroxyprogesterone 10 mg qd on day 22 of each cycle, and for the past two years has been free of premenstrual behavior changes, with only mild symptoms of restlessness and bloating. She is now working full time and married.


Premenstrual Syndrome is any combination of symptoms and signs occurring cyclically prior to menses and resolving with the onset of menses.

Clinical Presentation


The commonest symptoms are related to mood; - depression, irritability, tension, lability, lassitude, insomnia and impulsivity; to body fluid changes; - edema, weight gain, abdominal bloating, and breast fullness; and to physical discomfort - headache, breast pain, abdominal pain or generalized physical dysphoria.

Polydipsia, polyphagia, diarrhea and acne are also common. Pre-existing physical and emotional problems may be exacerbated.


Weight gain is common, but so is weight loss, and affect changes may be apparent in familiar patients. Laboratory investigations are not generally helpful.

Clinical Management


Almost all women report some premenstrual symptoms. It is essential to differentiate between those who find their symptoms tolerable, and those who consider themselves ill and who have distressing symptoms and impaired functional capacity. It is also important to assess any exacerbation of ongoing health problems. The specific symptoms most troublesome to the patient and their severity guide rational therapy.


The large number of theoretical models of the biochemical basis of PMS reflect the fragile, incomplete understanding of the problem and the complexity of its causative mechanisms. Likewise, the large number of recommended treatments, none of which are consistently effective, suggest a multiplicity of mechanisms with variable expression from patient to patient. In general terms, PMS seems to represent protean manifestations of psycho-neuro-endocrine flux, or dysfunction in the cycling of the hypothalamic-pituitary-ovarian axis. Particular symptoms suggest a role for specific mediators and provide some rationale for management of individual cases.

Estrogen effects sodium and water retention, and in addition alters the metabolism of plasma renin and angiotesin II with a resultant increase in Aldosterone

Progesterone has a natriuretic effect, but also increases aldosterone activity. PMS symptoms do not occur when physiologic progesterone levels are low in the pre-ovulatory phase and anovulatory cycles. Paradoxically, progesterone frequently is effective treatment. Although excreted levels of estrogren and progesterone are not measurably abnormal, an imbalance of estrogen/progesterone is a currently favored hypothesis. Further confusing this is the observation that as many patients are made worse as are made better with OCs.

Prolactin and vasopressin secretion may play a role in breast and fluid balance changes, and although plasma levels have not correlated with symptoms, normal bromocriptine has been beneficial, as have ergot alkaloids.

Changes in central catecholamines (dopamine, norepinephrine, and epinephrine) may play a role in affective and fluid balance changes.

The measurable changes in other pituitary products - alpha MSH,GH,LH, FSH and Beta endorphin - which occur premenstrually probably contribute to the complexity of PMS.

Numerous clinical therapeutic trials have been provoked by such possible causal associations as Vitamin B6 with abnormal tryptophan metabolism and estrogen metabolism, by the anti-estrogenic effect of Vitamin A, and its effect on acne, by possible allergy to endogenous progresterone, and by catharsis as a means of eliminating fluid and unspecified toxin in constipated patients.


The goal of therapy is to reduce symptoms to a level which is tolerable to the patient and which does not impair her function. Treatment should be aimed at the specifically troublesome symptoms, and frequent follow up should gauge the effect on these symptoms and the patient's improvement in function. Treatment should be carefully matched to the patient's distress, as many suggested therapies have significant toxicity.

Documented weight gain can be rationally approached with spironolactone 25-50 mg b-tid, and if this fails, hydrochlorothiazide, 25-50 mg qd.

Headache, mastalgia, and generalized discomfort may be relieved with mild analgesics, and NSAIDs may be particularly useful with patients who also suffer from dysmenorrhea.

Non-specific measures such as local heat, rest, and sodium restriction may be helpful, as may exercise and weight loss which, in theory, may have a beneficial effect on estrogen metabolism.

In patients with sleep disturbance and depression, tricyclics and occasionally lithium may be indicated.

Bellergal, a combination of ergot, phenobarbitol, and belladonna, is a non-specific but frequently useful treatment for patients with irritability, breast tenderness, and abdominal bloating. Except in low dose for occasional use, tranquilizers are best avoided as they are entirely non-specific, even though they will reduce any patient's complaints about most symptoms.

Medroxy progesterone 10 mg daily during the symptomatic days, and progesterone suppositories are very frequently effective. The estrogen antagonist methyltestosterone is very effective, but rarely, if ever, indicated. Bromocriptine counteracts the osmoregulatory actions and breast stimulation of prolactin, but also has numerous poorly understood actions in the pituitary hyopthalamus and basal ganglia.

Follow Up

The fine adjustment of treatment against symptoms can generally be achieved in a few monthly visits.


Explanation that PMS is not pathologic, accompanied by support from the physician and from acquaintances with PMS is very helpful. The patient should understand the goals of treatment and be given the responsibility for adjustment of therapy.


Most women suffer some symptoms of PMS, and at least a third report significant incapacity. Psychiatric disturbance, crime and accidents are more frequent during the premenstrual period but still less frequent than the noncycling base line for males. The data, then, may suggest that women deteriorate toward the male level of functioning during the premenstrual period, or conversely that women have a syndrome of functional improvement during the rest of the cycle, with fewer seizures, fewer symptoms, less aberrant behavior, increased energy and self-esteem, and improved mood.


The very significant costs of functional disability, interpersonal discord, and personal distress may be greatly ameliorated with education, support, and carefully adjusted symptomatic treatment.

Learning Issues

In managing a problem with no consistent physical signs or laboratory abnormalities, it is essential to make an accurate assessment of the patient's function and symptomatic distress, to tailor treatment to these, and to set and move toward appropriate goals together with the patient.


Premenstrual Syndrome, Editorial; Lancet; December 1981, 1393-94.

Reid, R.L. and Yen, S.S.C. Premenstrual Syndrome; American Journal of Obstetrics and Gynecology; 139; 85-104. 1981.

Elsner, C.W., Bromocriptine in the Treatment of Premenstrual Tension Syndrome, Obstetrics and Gynecology; 56, 6; 723-26. 1980. in the pre-ovulatory phase and anovulatory cycles. Paradoxically, progesterone frequently is effective treatment. Although excreted levels of estrogren and progesterone are not measurably abnormal, an imbalance of estrogen/progesterone is a currently f

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