by: William Mann MD
\nUniv of North Dakota School of Medicine<\/p>\n
PREMENSTRUAL SYNDROME<\/p>\n
Case History<\/p>\n
An unemployed nulliparous 19-year-old woman was arrested for stabbing
\nher boyfriend while intoxicated. Menarche was at 13 years, and she had
\nbeen well with no behavioral problem until l5, when she began to
\nexhibit paroxysmal aberrant behavior including: slashing her wrists,
\nshoplifting, arson, promiscuity, alcohol intoxication, expulsion from
\nschool for assaulting teachers, and mutilation of her hands and feet
\nwith cuts and cigarette burns. In prison, prior to her next four
\nmenstrual periods, she assaulted a guard, tried to hang herself, cut her
\nwrists, and attempted to escape. During the rest of her cycle, she was
\ncooperative, rational, and penitent. All past episodes of aberrant
\nbehavior which could be accurately dated, occurred on a cycle length of
\n29+- 2.5 days.<\/p>\n
Initially in prison she was treated with Chlorpromazine 100mg bid and
\nfluphenazine injections 20 mg every 10 days. She stated that she felt
\na little calmer, but depressed, with continued cyclic suicidal impulses
\nand a wish to “escape from life”. On several occasions during the
\npremenstruum she requested that she be locked up alone and expressed
\nfear that she was going to lose control.<\/p>\n
She was started on medroxyprogesterone 10 mg qd on day 22 of each cycle,
\nand for the past two years has been free of premenstrual behavior
\nchanges, with only mild symptoms of restlessness and bloating. She is
\nnow working full time and married.<\/p>\n
Definition<\/p>\n
Premenstrual Syndrome is any combination of symptoms and signs occurring
\ncyclically prior to menses and resolving with the onset of menses.<\/p>\n
Clinical Presentation<\/p>\n
Subjective<\/p>\n
The commonest symptoms are related to mood; – depression, irritability,
\ntension, lability, lassitude, insomnia and impulsivity; to body fluid
\nchanges; – edema, weight gain, abdominal bloating, and breast fullness;
\nand to physical discomfort – headache, breast pain, abdominal pain or
\ngeneralized physical dysphoria.<\/p>\n
Polydipsia, polyphagia, diarrhea and acne are also common.
\nPre-existing physical and emotional problems may be exacerbated.<\/p>\n
Objective<\/p>\n
Weight gain is common, but so is weight loss, and affect changes may be
\napparent in familiar patients. Laboratory investigations are not
\ngenerally helpful.<\/p>\n
Clinical Management<\/p>\n
Assessment<\/p>\n
Almost all women report some premenstrual symptoms. It is essential to
\ndifferentiate between those who find their symptoms tolerable, and
\nthose who consider themselves ill and who have distressing symptoms and
\nimpaired functional capacity. It is also important to assess any
\nexacerbation of ongoing health problems. The specific symptoms most
\ntroublesome to the patient and their severity guide rational therapy.<\/p>\n
Mechanisms<\/p>\n
The large number of theoretical models of the biochemical basis of PMS
\nreflect the fragile, incomplete understanding of the problem and the
\ncomplexity of its causative mechanisms. Likewise, the large number of
\nrecommended treatments, none of which are consistently effective,
\nsuggest a multiplicity of mechanisms with variable expression from
\npatient to patient. In general terms, PMS seems to represent protean
\nmanifestations of psycho-neuro-endocrine flux, or dysfunction in the
\ncycling of the hypothalamic-pituitary-ovarian axis. Particular
\nsymptoms suggest a role for specific mediators and provide some
\nrationale for management of individual cases.<\/p>\n
Estrogen effects sodium and water retention, and in addition alters the
\nmetabolism of plasma renin and angiotesin II with a resultant increase
\nin Aldosterone<\/p>\n
Progesterone has a natriuretic effect, but also increases aldosterone
\nactivity. PMS symptoms do not occur when physiologic progesterone
\nlevels are low in the pre-ovulatory phase and anovulatory cycles.
\nParadoxically, progesterone frequently is effective treatment.
\nAlthough excreted levels of estrogren and progesterone are not
\nmeasurably abnormal, an imbalance of estrogen\/progesterone is a
\ncurrently favored hypothesis. Further confusing this is the
\nobservation that as many patients are made worse as are made better
\nwith OCs.<\/p>\n
Prolactin and vasopressin secretion may play a role in breast and fluid
\nbalance changes, and although plasma levels have not correlated with
\nsymptoms, normal bromocriptine has been beneficial, as have ergot
\nalkaloids.<\/p>\n
Changes in central catecholamines (dopamine, norepinephrine, and
\nepinephrine) may play a role in affective and fluid balance changes.<\/p>\n
The measurable changes in other pituitary products – alpha MSH,GH,LH,
\nFSH and Beta endorphin – which occur premenstrually probably contribute
\nto the complexity of PMS.<\/p>\n
Numerous clinical therapeutic trials have been provoked by such
\npossible causal associations as Vitamin B6 with abnormal tryptophan
\nmetabolism and estrogen metabolism, by the anti-estrogenic effect of
\nVitamin A, and its effect on acne, by possible allergy to endogenous
\nprogresterone, and by catharsis as a means of eliminating fluid and
\nunspecified toxin in constipated patients.<\/p>\n
Plans<\/p>\n
The goal of therapy is to reduce symptoms to a level which is tolerable
\nto the patient and which does not impair her function. Treatment
\nshould be aimed at the specifically troublesome symptoms, and frequent
\nfollow up should gauge the effect on these symptoms and the patient’s
\nimprovement in function. Treatment should be carefully matched to the
\npatient’s distress, as many suggested therapies have significant
\ntoxicity.<\/p>\n
Documented weight gain can be rationally approached with spironolactone
\n25-50 mg b-tid, and if this fails, hydrochlorothiazide, 25-50 mg qd.<\/p>\n
Headache, mastalgia, and generalized discomfort may be relieved with
\nmild analgesics, and NSAIDs may be particularly useful with patients
\nwho also suffer from dysmenorrhea.<\/p>\n
Non-specific measures such as local heat, rest, and sodium restriction
\nmay be helpful, as may exercise and weight loss which, in theory, may
\nhave a beneficial effect on estrogen metabolism.<\/p>\n
In patients with sleep disturbance and depression, tricyclics and
\noccasionally lithium may be indicated.<\/p>\n
Bellergal, a combination of ergot, phenobarbitol, and belladonna, is a
\nnon-specific but frequently useful treatment for patients with
\nirritability, breast tenderness, and abdominal bloating. Except in low
\ndose for occasional use, tranquilizers are best avoided as they are
\nentirely non-specific, even though they will reduce any patient’s
\ncomplaints about most symptoms.<\/p>\n
Medroxy progesterone 10 mg daily during the symptomatic days, and
\nprogesterone suppositories are very frequently effective. The estrogen
\nantagonist methyltestosterone is very effective, but rarely, if ever,
\nindicated. Bromocriptine counteracts the osmoregulatory actions and
\nbreast stimulation of prolactin, but also has numerous poorly
\nunderstood actions in the pituitary hyopthalamus and basal ganglia.<\/p>\n
Follow Up<\/p>\n
The fine adjustment of treatment against symptoms can generally be
\nachieved in a few monthly visits.<\/p>\n
Education<\/p>\n
Explanation that PMS is not pathologic, accompanied by support from the
\nphysician and from acquaintances with PMS is very helpful. The patient
\nshould understand the goals of treatment and be given the
\nresponsibility for adjustment of therapy.<\/p>\n
Epidmiology<\/p>\n
Most women suffer some symptoms of PMS, and at least a third report
\nsignificant incapacity. Psychiatric disturbance, crime and accidents
\nare more frequent during the premenstrual period but still less
\nfrequent than the noncycling base line for males. The data, then, may
\nsuggest that women deteriorate toward the male level of functioning
\nduring the premenstrual period, or conversely that women have a
\nsyndrome of functional improvement during the rest of the cycle, with
\nfewer seizures, fewer symptoms, less aberrant behavior, increased
\nenergy and self-esteem, and improved mood.<\/p>\n
Costs<\/p>\n
The very significant costs of functional disability, interpersonal
\ndiscord, and personal distress may be greatly ameliorated with
\neducation, support, and carefully adjusted symptomatic treatment.<\/p>\n
Learning Issues<\/p>\n
In managing a problem with no consistent physical signs or laboratory
\nabnormalities, it is essential to make an accurate assessment of the
\npatient’s function and symptomatic distress, to tailor treatment to
\nthese, and to set and move toward appropriate goals together with the
\npatient.<\/p>\n
References<\/p>\n
Premenstrual Syndrome, Editorial; Lancet; December 1981, 1393-94.<\/p>\n
Reid, R.L. and Yen, S.S.C. Premenstrual Syndrome; American Journal of
\nObstetrics and Gynecology; 139; 85-104. 1981.<\/p>\n
Elsner, C.W., et.al. Bromocriptine in the Treatment of Premenstrual
\nTension Syndrome, Obstetrics and Gynecology; 56, 6; 723-26. 1980.
\nin the pre-ovulatory phase and anovulatory cycles.
\nParadoxically, progesterone frequently is effective treatment.
\nAlthough excreted levels of estrogren and progesterone are not
\nmeasurably abnormal, an imbalance of estrogen\/progesterone is a
\ncurrently f<\/p>\n
