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Journal ArticleDOI

Premenstrual Syndromes—An Approach to Diagnosis and Treatment

05 Mar 2007-South African Family Practice (Taylor & Francis)-Vol. 49, Iss: 3, pp 20-22

Abstract: This article discusses the differences between premenstrual syndrome and premenstrual dysphoric disorder and outlines a treatment approach.

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SA Fam Pract 2007:49(3)
20
SA Fam Pract 2007:49(3)
21
Premenstrual Syndromes - An Approach to
Diagnosis and Treatment
Swart P, MBChB, MMed (O & G)
Dreyer G, MBChB, MMed (O & G)
Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria
Correspondence to: Prof Greta Dreyer, E-mail: gretadreyer@mweb.co.za
Abstract
SA Fam Pract 2007;49(3): 20-22
CPD Article
INTRODUCTION
The premenstrual syndromes are char-
acterised by physical and/or affective
symptoms that occur in the luteal phase
of the menstrual cycle. Symptoms and
severity of symptoms vary and therefore
the impact of these syndromes on psy-
chosocial and economical aspects is
difficult to quantify and generalise.
CLINICAL MANIFESTATIONS
Premenstrual syndrome (PMS) will af-
fect about 25% of women with a regular
menstrual cycle, depending on the
strictness of criteria. Physical and be-
havioural symptoms can occur.
Premenstrual dysphoric disorder
(PMDD) is a more severe type of
PMS where the psychological and
behavioural symptoms of labile and
depressed mood, anger, irritability and
internal tension are prominent. PMDD
occurs in about 5% of women with regu-
lar cycles.
1
While over 150 symptoms have been
ascribed to PMS, the most common
symptoms are listed in tables 1 and 2.
To accurately diagnose these disorders,
recognized criteria should be used as
many women suffer from other underly-
ing disorders exacerbated pre-menstru-
ally and should not be treated as PMS.
2
DIAGNOSTIC CRITERIA
The criteria of the American College
of Obstetricians and Gynecologists for
PMS are widely used (table 2). These
criteria describe affective and somatic
symptoms in a cyclical fashion with a
severity criterion of identifiable social or
economic dysfunction.
3
For the diagnosis of PMDD the most
widely used criteria is that of the DSM-IV
(table 3).
Only affective symptoms are required
with prospective confirmation, correct
timing and a severity clause.
4
PATHOGENESIS
Ovarian steroid hormone fluctuations
are clearly needed to precipitate the
symptoms. On the other hand it is also
clear that these cyclical changes are not
solely responsible for either the mood
changes or the systemic manifestations
of the syndrome and disorder. Suscep-
tible symptomatic women have levels
comparable to levels found in asymp-
tomatic women.
5
Interaction between the ovarian ste-
roid hormones and neurotransmitters
seems to play a major role, with sero-
tonin currently most implicated. While
susceptibility to both mood disorders
Table 2: The diagnostic criteria of the American College of Obstetricians and Gynecologists
for premenstrual syndrome.
Table 1: Common symptoms of premenstrual
syndrome.
COMMON PHYSICAL SYMPTOMS
OF PMS
Abdominal bloating
Extreme fatigue
Breast tenderness
Headache
Also: acne, dizziness, palpitations,
gastro-intestinal upset
COMMON BEHAVIOURAL SYMPTOMS
OF PMS
Labile mood
Irritability
Tensions
Depressed mood
Also: anger, increased appetite, easy
crying, forgetfulness
DIAGNOSTIC CRITERIA FOR PREMENSTRUAL SYNDROME
* At least one of the following affective and somatic symptoms must be reported during
the five days before menses in each of the three prior menstrual cycles:
Affective Symptoms
- Depression
- Angry outbursts
- Irritability
- Anxiety
- Confusion
- Social Withdrawal
Somatic Symptoms
- Breast tenderness
- Abdominal bloating
- Headache
- Swelling of extremities
* These symptoms are relieved within 4 days of the onset of menses without recurrence
until at least cycle day 13.
* The symptoms are present in the absence of any pharmacologic therapy, hormone
ingestion, or drug or alcohol use.
* The symptoms occur reproducibly during two cycles of prospective recording.
* The patient suffers from identifiable dysfunction in social or economic performance.
This article discusses the differences between premenstrual syndrome and premenstrual dysphoric disorder and outlines a
treatment approach.

SA Fam Pract 2007:49(3)
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SA Fam Pract 2007:49(3)
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CPD Article
and PMS and PMDD are strongly in-
herited, predisposition to other mood
disorders do not seem to predict PMS/
PMDD.
6
Steroid hormone fluctuations indeed
cause cyclical change in the opoid
system (beta-endorphin), the GABA
system and the serotonin system cen-
trally.
7,8
It appears that the fluctuations
caused in these neurotransmitters are
accentuated in women suffering symp-
toms of PMS/PMDD, pointing towards
increased biological sensitivity to cycli-
cal change.
9,10
This genetically determined bio-
logical vulnerability is most likely also
affected by personal and social factors
influencing the severity of symptoms.
Several recent studies, however, have
challenged the importance of external
factors like psychosocial stress.
11,12
TREATMENT
Premenstrual symptoms are common
and do not need treatment, the premen-
strual syndrome (PMS), however is less
common and more frequently would
need intervention. The premenstrual
dysphoric disorder (PMDD) is much
less common and would mostly need
treatment. Because these disorders
are not easy to diagnose, the symptoms
frequently not easy to quantify, the
response to treatment is also not easy
to measure. Patients would commonly
perceive their symptoms as varying
substantially from month to month and
this makes the response to treatment
even more difficult to judge.
It would be important to explain to
patients who present with this syndrome
complex that the problem is not caused
by an abnormality in hormone secretion.
It is also important to point out that this
problem is not as easily treatable as
pneumonia where one can use a course
of antibiotics that solves the disease
permanently. The treatment plan would
virtually always be a long-term plan.
Different treatment options will be
discussed with the evidence for pre-
scribing these therapies.
Serotonin Reuptake Inhibitors
This group of drugs probably have the
best evidence for being effective in this
syndrome. The efficacy of particularly
fluoxetine has been documented in quite
a number of studies. The typical positive
response rate is as high as 75%, with the
usual prescribed dosage 20mg per day.
A higher dose is not more effective and
significantly increases the side effects.
It is also important to note from these
trials that both the affective and somatic
symptoms improve on this drug and
that the response is maintained over the
long term.
13,
14
Fluoxetine is approved
by the FDA for PMDD but not by the Eu-
ropean drug regulators because of their
concern with lack of strict diagnostic
criteria in certain trials and their concern
with possible inappropriate prescribing
practices. There are also publications
to support the use of other SRI’s such as
paroxetine and citalopram.
Only administering the drugs during
the luteal phase is also supported by
placebo controlled trials and might well
be the better option to reduce side-ef-
fects and cost. The drug would typically
be given from about day 14 to the first
day of menstruation.
15
Physical symp-
toms might not respond as well on the
intermittent regime as continuous use.
Antidepressants not belonging to the
group of SRI’s such as MAOI’s and the
tricyclic antidepressants are unfortu-
nately not effective in this condition. The
same is true for lithium. These drugs do
not fare better than placebo in trials and
should not be used.
Benzodiazepines
Alprazolam may be beneficial in women
with PMS but does not seem to work
well in patients that suffer from PMDD.
It would not be the first drug to use and
the addictive potential is real.
16,17,18
Oral Contraceptives
Inducing anovulation should alleviate
the symptoms of this disease but sev-
eral studies failed to show any improve-
ment using some of the older formula-
tions. There are however more than one
placebo controlled trial where the newer
progestogen drosperinone was used.
In both the contraceptive formulations
that contain drosperinone (with 24
and 21 day active tablets) statistically
significant beneficial effects have been
shown.
19,20
GnRH analogues
By inducing anovulation with these
agents a woman is relieved from all
hormonal fluctuations and PMS/PMDD
will improve. It is more effective in
preventing physical and irritability
symptoms than depressive symptoms.
Unfortunately side effects such as
flushing and emotional sequelae are
common. Add-back therapy to control
the hypo-estrogenic symptoms will give
protection against the flushing and bone
RESEARCH CRITERIA FOR PREMENSTRUAL DYSPHORIC DISORDER
A) In most menstrual cycles during the past five year, five (or more) of the
following symptoms were present for most of the time during the last week
of the luteal phase, began to remit within a few days after the onset of the
follicular phase, and were absent in the week post menses, with at least one
of the symptoms being either of the first four:
1. Markedly depressed mood, feelings of hopelessness, or self-deprecating
thoughts
2. Marked anxiety, tension, feelings of being “keyed up” of “on edge”
3. Marked affective liability (e.g., feeling suddenly sad or tearful or increased
sensitivity to rejection)
4. Persistent and marked anger or irritability or increased interpersonal conflicts
5. Decreased interest in usual activities (e.g., work, school friends, hobbies)
6. Subjective sense of difficulty in concentrating
7. Lethargy, easy fatigability, or marked lack of energy
8. Marked change in appetite, overeating, or specific food cravings
9. Hypersomnia or insomnia
10. A subjective sense of being overwhelmed or out of control
11. Other physical symptoms, such as breast tenderness or swelling, headaches,
joint or muscle pain, a sensation of “bloating”, weight gain
B) The disturbance markedly interferes with work or school or with usual social
activities and relationships with others (e.g., avoidance of social activities,
decreased productivity and efficiency at work or school).
C) The disturbance is not merely an exacerbation of the symptoms of another disorder,
such as Major Depressive Disorder, Panic Disorder, Dysthymic Disorder, or a
Personality Disorder (although it may be superimposed on any of these disorders).
D) Criteria A, B, and C must be confirmed by prospective daily ratings during at least
two consecutive symptomatic cycles. (The diagnosis may be made provisionally
prior to this confirmation.)
Table 3: The DSM IV diagnostic criteria of the Amercian Psychiatric Association. (Diagnostic
and Statistical Manual Edition IV)

SA Fam Pract 2007:49(3)
22
CPD Article
loss but still does not make this a viable
option in the long term. It could however
be used to predict the effect of surgical
oophorectomy.
21,22,23
Danazol
Danazol does improve the symptoms
but only once high enough dosages
are used to suppress ovulation. Unfor-
tunately the androgenic side effects are
too severe at these dosages for most
patients.
Spironolactone
This steroid like diuretic should have the
best likelihood to be effective but results
of trials are at best ambiguous.
Exercise
It is difficult to investigate this option in a
blinded manner but trials and observa-
tional data suggest a beneficial effect.
Exercise should be recommended.
Calcium
There are studies that show a beneficial
response on calcium supplementation if
600mg twice daily is used. Other stud-
ies show a dose related association
between intake and severity of symp-
toms.
24
Other Supplements
The response on vitamin B6 is at best not
dramatic but it might well be worth try-
ing.
25
Magnesium supplementation has
even less convincing scientific evidence
but small trials have described modest
improvements. Vitamin E supplementa-
tion at 400IU per day was described in
small studies to improve the physical
and affective symptoms.
Evening Primrose oil, gingko biloba
and essential free fatty acids really have
no evidence to show their efficacy and
progesterone has been shown not to
work.
SUGGESTED APPROACH TO MAN-
AGEMENT:
In patients where the diagnosis has
been established and the woman is
symptom free in the follicular phase,
it would be important to quantify her
symptoms. If the situation is manage-
able the patient should be advised to
exercise in a scheduled program with
significant intensity. Vitamin B6 should
probably be offered as it might work and
is harmless as long as doses not more
than 100mg per day is used.
If distress is judged to be severe
SRI’s should be offered. About 30%
of patients will not respond to SRI’s and
it might be worth while increasing the
dose, changing to a 2
nd
SRI or switching
from luteal phase therapy to continuous
therapy. A few patients will have signifi-
cant side effects such as nausea, head-
ache, poor libido and anorgasmia.
Drosperinone containing contracep-
tives should frequently be used and in
recalcitrant cases alprazolam, spirono-
lactone and calcium supplements might
offer some relief. As an absolute last
resort and when GnRH has been suc-
cessful in alleviating symptoms removal
of the uterus and ovaries should be con-
templated.
See CPD Questionnaire, page 39
P This article has been peer reviewed
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References
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TL;DR: In women with premenstrual syndrome, the occurrence of symptoms represents an abnormal response to normal hormonal changes.
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TL;DR: SSRIs were effective in treating physical and behavioural symptoms and there was no significant difference in symptom reduction between continuous and intermittent dosing or between trials funded by pharmaceutical companies and those independently funded.
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TL;DR: SSRIs were found to be highly effective in treating premenstrual symptoms and there was no significant difference between trials funded by pharmaceutical companies and those independently funded.
Abstract: Background Premenstrual syndrome (PMS) is a common cause of physical, psychological and social problems in women of reproductive age. The key characteristic of PMS is the timing of symptoms, which occur only during the two weeks leading up to menstruation (the luteal phase of the menstrual cycle). Selective serotonin reuptake inhibitors (SSRIs) are increasingly used as first line therapy for PMS. SSRIs can be taken either in the luteal phase or else continuously (every day). SSRIs are generally considered to be effective for reducing premenstrual symptoms but they can cause adverse effects. Objectives The objective of this review was to evaluate the effectiveness and safety of SSRIs for treating premenstrual syndrome. Search methods Electronic searches for relevant randomised controlled trials (RCTs) were undertaken in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycINFO, and CINAHL (February 2013). Where insufficient data were presented in a report, attempts were made to contact the original authors for further details. Selection criteria Studies were considered in which women with a prospective diagnosis of PMS, PMDD or late luteal phase dysphoric disorder (LPDD) were randomised to receive SSRIs or placebo for the treatment of premenstrual syndrome. Data collection and analysis Two review authors independently selected the studies, assessed eligible studies for risk of bias, and extracted data on premenstrual symptoms and adverse effects. Studies were pooled using random-effects models. Standardised mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for premenstrual symptom scores, using separate analyses for different types of continuous data (that is end scores and change scores). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes. Analyses were stratified by type of drug administration (luteal or continuous) and by drug dose (low, medium, or high). We calculated the number of women who would need to be taking a moderate dose of SSRI in order to cause one additional adverse event (number needed to harm: NNH). The overall quality of the evidence for the main findings was assessed using the GRADE working group methods. Main results Thirty-one RCTs were included in the review. They compared fluoxetine, paroxetine, sertraline, escitalopram and citalopram versus placebo. SSRIs reduced overall self-rated symptoms significantly more effectively than placebo. The effect size was moderate when studies reporting end scores were pooled (for moderate dose SSRIs: SMD -0.65, 95% CI -0.46 to -0.84, nine studies, 1276 women; moderate heterogeneity (I2 = 58%), low quality evidence). The effect size was small when studies reporting change scores were pooled (for moderate dose SSRIs: SMD -0.36, 95% CI -0.20 to -0.51, four studies, 657 women; low heterogeneity (I2=29%), moderate quality evidence). SSRIs were effective for symptom relief whether taken only in the luteal phase or continuously, with no clear evidence of a difference in effectiveness between these modes of administration. However, few studies directly compared luteal and continuous regimens and more evidence is needed on this question. Withdrawals due to adverse effects were significantly more likely to occur in the SSRI group (moderate dose: OR 2.55, 95% CI 1.84 to 3.53, 15 studies, 2447 women; no heterogeneity (I2 = 0%), moderate quality evidence). The most common side effects associated with a moderate dose of SSRIs were nausea (NNH = 7), asthenia or decreased energy (NNH = 9), somnolence (NNH = 13), fatigue (NNH = 14), decreased libido (NNH = 14) and sweating (NNH = 14). In secondary analyses, SSRIs were effective for treating specific types of symptoms (that is psychological, physical and functional symptoms, and irritability). Adverse effects were dose-related. The overall quality of the evidence was low to moderate, the main weakness in the included studies being poor reporting of methods. Heterogeneity was low or absent for most outcomes, though (as noted above) there was moderate heterogeneity for one of the primary analyses. Authors' conclusions SSRIs are effective in reducing the symptoms of PMS, whether taken in the luteal phase only or continuously. Adverse effects are relatively frequent, the most common being nausea and asthenia. Adverse effects are dose-dependent.

236 citations