Premenstrual Syndrome: An Overview

Name: premenstrual syndrome

Synonyms: PMS, premenstrual dysphoric disorder, PMDD, late luteal phase dysphoria, premenstrual tension, General
description This syndrome refers to a complex of physical and mood symptoms that worsen in the one to two weeks prior to a woman's menses and disappear by the end of a full menstrual flow.

Behavioral symptoms commonly include:

fatigue
irritability
labile mood (anger/sadness)
depression
oversensitivity
crying spells
social withdrawal
forgetfulness
difficulty concentrating

Physical symptoms commonly include:

abdominal pelvic bloating
breast tenderness
acne flare up
appetite changes
food cravings
extremity swelling
headache
stomach upset

Is it common?

About 80% of women report premenstrual emotional and physical changes. About 20-40% of these women experience difficulty with these symptoms so that there is some change in behavior that is noticeable by themselves and others. This group would be considered to have menstrual distress.

Approximately 3-5% of women in the reproductive age group report a significant impact of these symptoms on work, lifestyle or relationships. This degree of severity is called premenstrual syndrome (1).

Some authors have tried to divide PMS into 3 severity stages: low level symptoms, PMS regular or standard symptoms (menstrual distress), and premenstrual magnification symptoms (2, 3, 4). The latter would be identified by most physicians as PMS.

Differentiating features

Mood and physical symptom questionnaires in the follicular phase (days 4-9) and the luteal phase (days 22-27) of the menstrual cycle or a prospective symptom calendar tracking 4 or more prominent symptoms is necessary to differentiate this condition from other medical and psychologic conditions which may just worsen somewhat with menstrual physiology. There should be a symptom free interval from about day 4 to day 12 of a menstrual cycle and at least a 30% higher symptom score in the last 7 days before a menstrual period (1).

Other mental health and medical conditions need to be ruled out as underlying problems:

Mental health disorders

major depression
minor depression (dysthymia)
generalized anxiety
panic disorder
bipolar illness (mood irritability)

Medical disorders

anemia
autoimmune disorders
hypothyroidism
diabetes
seizure disorders
endometriosis
chronic fatigue syndrome
collagen vascular disease

A serum TSH to check thyroid function and a screening inventory for depression, anxiety disorder and panic disorder have the highest yield to rule out the most commonly confusing conditions.

Other features Painful menstrual cramps (dysmenorrhea) may present with PMS but they are not usually considered to be a part of the syndrome and probably have a different etiology. Breast soreness (mastalgia) can go along with PMS but it often occurs as a separate condition without accompanying mood problems.

It is estimated that as many as 50-60% of women with the complaint of severe PMS have other medical or psychiatric conditions. Over 150 symptoms have been attributed to PMS so the symptom list can be extensive. It can even include hot flashes, heart palpitations and dizziness (1).

Cause

Premenstrual syndrome does not occur in women before menarche (start of menses), after menopause or without ovulation. It takes ovulatory menstrual cycles to have PMS. Evidence supports the theory that premenstrual symptoms are caused primarily by changes in brain chemicals that transmit between nerves and cells (neurotransmitters) brought about by cyclical fluctuations in ovarian hormones.

An ovulatory cycle has slightly higher estrogen and massively higher progesterone levels in the two weeks before a menses than in the two weeks after a menses. There is some debate as to whether progesterone causes or relieves PMS symptoms (5, 6, 7, 8, 9), but the consensus seems to be that progesterone and synthetic progestins can cause PMS types of mood symptoms (10). Since progesterone and progestins can also relieve symptoms it seems best not to prejudge its role in the cause of PMS. It is interesting that anti progesterone drugs (RU-486) do not make the symptoms go away (11).

Studies have looked at whether the hormones in the luteal phase are at different levels in women with and without PMS. Essentially they found no differences in estrogen and progesterone levels. Cortisol, which is a stress hormone is lower in women with severe PMS symptoms but this is more likely an effect than a cause, i.e., the stress hormone has been depleted by the stress (12, 13). Thyroid hormone has been looked at and except for the about 5% incidence of hypothyroidism found in women presenting for PMS, abnormal thyroid function has not been found to be associated with premenstrual syndrome (14).

Unnecessary studies

Serum blood measurements of estradiol (estrogens), progesterone, or testosterone.

Natural history untreated In the age range of 25-45, PMS symptoms develop and quickly peak within several months. After that they tend to stay at a fixed level and not progressively worsen as do some of the other medical or mental health conditions. Unless the symptoms are treated in some manner, they stay the same until menopause when the cyclicity goes away as ovulation stops.

Goals of therapy (Rx)

The main goal of treating PMS symptoms is to reduce those symptoms in intensity to the point where they do not cause difficulty with family and work relationships, they do not cause time lost from work or leisure activities, and they do not cause a woman to alter her daily activities just because of where she is in the menstrual cycle.

1st choice therapy

After the diagnosis of PMS without underlying medical or mental health problems is confirmed, the primary treatment is lifestyle changes aimed at reducing the overall baseline stress level. This means discontinuance of all caffeine and alcohol which are known to aggravate stress states (15, 16, 17, 18), beginning a restricted diet such as a low fat, vegetarian or high complex carbohydrate diet (19), and starting a regular exercise or conditioning program (20, 21). All of these need to be instituted before additional over-the-counter or prescription treatment is begun.

If prescription medication is needed, fluoxetine (Prozac®), 10-20 mg/day is effective with low side effects.

Other therapies used

Effective non prescription treatments include:

Vitamin B-6 up to 100 mg/day (22)
Calcium 1000 mg/day (calcium carbonate)(23)
Magnesium (Mg) 200 mg/day as MgO (24)
Naproxen sodium 550 mg twice a day (eg, Alleve®)(25)

Effective prescription therapies include:

fluoxetine (Prozac®)(26) 20 mg/day
sertraline (Zoloft®)(27) 50-150 mg/day
paroxetine (Paxil®)(28, 29)10-30 mg/day
clomipramine (Anafranil®)(30, 31) 25-75 mg/day (14 days before menses)
alprazolam (Xanax®)(32, 33, 34) 0.25 mg/ 3-4 times/day (6-14 days before menses)
buspirone (Buspar®) 25-60 mg/day (12 days before menses)
GnRH agonist Lupron®(35, 36, 37) 3.75 - 7.5 mg/monthly I.M.
GnRH agonist Buserelin (38) 400-900 ug/day intranasal
propanolol (39) 20 mg/day between menses and 40 mg/day during menses

Removal of both the uterus and ovaries cures PMS (40, 41) but this is generally not an option for younger women. PMS symptoms do not always return following a hysterectomy with oopherectomy for PMS if replacement hormones are given after surgery (42). By itself, hysterectomy without removing the ovaries does not cure PMS but it often decreases many of the physical symptoms to a point where a woman can tolerate the remaining cyclical symptoms (43). In general, 75% of women who have a hysterectomy without oophorectomy will be permanently relieved of their symptoms, while 25% will still complain of PMS (44).

Treatments to avoid

Herbal treatments have not yet been shown to be effective for PMS.

Progesterone efficacy has conflicting studies and since many women get mood side effects from progesterone and progestins, these are not used as treatment. For the same reason birth control pills and progesterone shots such as depomedroxyprogesterone acetate (DepoProvera®) may be used since they block ovulation, but some women have worsened symptoms on these treatments.

Reason for Rx choices

While all of the above non prescription and prescription treatments are effective, in a clinical trial comparing vitamin B6, alprazolam, and propanolol with fluoxetine (Prozac®) 10 mg/day, fluoxetine had slightly less side effects and was slightly more efficacious in reducing symptoms (by 65%) than the other drugs (39).