Premenstrual Syndrome

1. PREMENSTRUAL SYNDROME
CHASING AWAY THE MONTHLY BLUES
DR LAU NGEE YIN
DEPARTMENT OF OBSTETRICS & GYNAECOLOGY
SARAWAK GENERAL HOSPITAL
O&G UPDATE 6TH MAY 2017

2. INTRODUCTION & BACKGROUND
EPIDEMIOLOGY
• PMS encompasses a vast array of psychological symptoms such
as depression, anxiety, irritability, loss of condence and mood
swings.
• There are also physical symptoms, typically bloatedness and
mastalgia.
• It is the timing, rather than the types of symptoms, and the
degree of impact on daily activity that supports a diagnosis of
PMS.
• Four in ten women (40%) experience symptoms of PMS and of
these 5–8% suffer from severe PMS.

3. AETIOLOGY
• Although the aetiology remains uncertain, it revolves around the
ovarian hormone cycle, which is reinforced by the absence of PMS
prior to puberty, during pregnancy and after the menopause.
• Currently two theories predominate and appear interlinked.
• The first suggests that some women are ‘sensitive’ to progesterone
and progestogens, since the serum concentrations of estrogen or
progesterone are the same in those with or without PMS.
• The second theory implicates the neurotransmitters serotonin and c-
aminobutyric acid (GABA). Serotonin receptors are responsive to
estrogen and progesterone, and selective serotonin reuptake
inhibitors (SSRIs) are proven to reduce PMS symptoms. GABA levels
are modulated by the metabolite of progesterone, allopregnanolone,
and in women with PMS the allopregnanolone levels appear to be

4. CLASSIFICATION OF PMS (ISPMD
CONSENSUS)
1. Physiological premenstrual symptoms (mild premenstrual
disorder)
2. Core premenstrual disorder
3. Premenstrual disorder, absent menstruation
4. Progestogen-induced premenstrual disorder
5. Premenstrual exacerbation (PME)
6. Mis-attribution

5. • Physiological premenstrual
symptoms (mild premenstrual
disorder)
- Occurs in a cyclical nature
with a symptom free week in
the follicular phase. The severity
of these symptoms is not great
enough to have a serious
impact on the quality of life,
but is noticeable to the patient

6. • Core premenstrual disorder
-Symptoms occur in a cyclical pattern with onset following
ovulation and must be resolved during or shortly after
menstruation to give at least one symptom free week; this
timing is a key characteristic of core premenstrual disorder. The
severity of these symptoms is great enough to cause significant
impairment and have a serious impact on the quality of life.
- Based on symptoms, core premenstrual disorders are further
subdivided into:
- predominantly psychological symptoms*
- predominantly somatic symptoms
- mixed both psychological and somatic symptoms.*

7. • Premenstrual disorder, absent
menstruation
- Essentially the same as core
premenstrual disorder but without
menstruation as a reference point
to ensure resolution of symptoms
following menstruation. This results
from continued ovarian activity
when iatrogenic amenorrhoea is
caused by hysterectomy,
endometrial ablation or the
levonorgestrel intrauterine device.

8. • Progestogen-induced
premenstrual disorder
- Symptoms are cyclical
and result directly from
treatment with exogenous
progestogens, e.g.
hormone replacement
therapy or hormonal
contraceptives, not
ovulation.

9. • Premenstrual exacerbation
(PME)
- This is the worsening of a
medical, psychological or
physical condition (e.g.
depression, asthma or
epilepsy) during the
premenstrual phase causing
substantial impairment.
Symptoms still follow a
cyclical pattern but are not
fully resolved by the end of
menstruation.

10. • Mis-attribution
- If symptoms are not
cyclical (i.e. are not relieved
by menstruation), the patient
does not have a
premenstrual disorder and
may instead have a
continuous psychological or
physical disorder which
requires appropriate
treatment.

11. SYMPTOMS & DIAGNOSIS
• There are over 200 reported premenstrual symptoms. The
timing of these symptoms is more important than their
character.
• Physical symptoms:
• breast tenderness or pain
• abdominal swelling or bloating
• headaches
• skin disorders
• weight gain
• swelling of extremities (hands or feet or both)
• joint pain, muscle pain, back pain.

12. SYMPTOMS & DIAGNOSIS
• Psychological and behavioural symptoms:
• mood swings (e.g. feeling suddenly sad or crying, increased
sensitivity to rejection)
• irritability
• anger, aggression
• anxiety
• depressed mood
• confusion
• tension
• sleep disturbances

13. SYMPTOMS & DIAGNOSIS
• changes in appetite, overeating or specific food cravings
• fatigue, lethargy, or lack of energy
• restlessness
• poor concentration
• social withdrawal
• not in control
• lack of interest in usual activities
• loneliness
• hopelessness.

14. SYMPTOMS & DIAGNOSIS
• It is essential to take a detailed patient history as well as
a daily prospective symptom rating over TWO consecutive
menstrual cycles.
• The RCOG recommends the Daily Record of Severity of
Problems (DRSP).

16. TREATMENT
• Treatment strategy is governed by the premenstrual
disorder diagnosis.
• Mild premenstrual disorder
- As the impact of premenstrual symptoms does not
impede daily life, it is recommended that support,
reassurance and guidance of good nutrition, exercise and
stress reduction are provided to women who fall into this
category.

17. TREATMENT – CORE PREMENSTRUAL
DISORDER• Core premenstrual disorder
-Overall there are two broad approaches involving either
the suppression or non-suppression of ovulation.
1. Treatment by supression of ovulation
Potential treatments to supress ovulation include:
GnRH agonists
the combined oral contraceptive pill
danazol
estrogen
surgery.

18. 2. Treatment without ovulation suppression includes:
serotonin re-uptake inhibitors
diuretics
non-pharmaceutical drug based treatments.

19. THE COMBINED ORAL CONTRACEPTIVE
PILL
• Yasmin® and Yaz® (Bayer Schering Pharma) are examples of
a drosperinone-containing COCP.
• RCTs showing the therapeutic efficacy of COCPs which
contain drospirenone, an antimineralocorticoid and
antiandrogenic progestogen.
• COCPs should be one of the first-line treatments for core
premenstrual disorder as long as there is no
contraindication for COCP use.

20. GNRH AGONISTS
• In premenstrual disorders it serves the following purposes:
• it allows us to determine what proportion of symptoms is of
ovarian endocrine origin
• it pinpoints which women with severe premenstrual disorder would
benefit from bilateral oophorectomy (relevant particularly where a
woman is to undergo hysterectomy for another gynaecological
indication)
• it may be useful combined with add-back in women in whom
estrogens are contraindicated and who will shortly reach the
menopause.
• GnRH agonists do not prevent pregnancy, so contraception must also
be addressed in the treatment plan.
• GnRH analogues would not be considered first line therapy, as even
with add-back therapy there may be health implications.

21. DANAZOL
• A meta-analysis showed that danazol in doses that
suppress ovulation is effective for many premenstrual
disorder symptoms particularly for cyclical mastalgia.
Unfortunately, this drug has limited use in the long term
because of its androgenic side effects, particularly those
on the lipid profile.
• When (rarely) it is used, contraception is required during
its use as it can cause virilisation of a developing female
foetus.

22. ESTROGEN
• There is good evidence showing that ovulation suppression
with estradiol implants or patches (100 and 200 mcg) can
effectively treat core premenstrual disorders.
• Estrogen alone may lead to endometrial hyperplasia. This
can sometimes be avoided by administering the
progestagen via the intrauterine route (levonorgestrel IUS)
when systemic levels and CNS stimulation are minimal.

23. SURGERY
• Hysterectomy alone or endometrial ablation will not
eliminate premenstrual symptoms because ovarian function
is conserved. Bilateral oophorectomy may be requested by
women with severe premenstrual disorder.
• 'GnRH agonist test' is advisable, though it has not been
scientifically proven, to test whether permanent ovulation
suppression would be a successful treatment strategy.
Following surgery, estrogen replacement should be provided
up until the time of natural menopause.

24. TREATMENT WITHOUT OVULATION
SUPPRESSION - SEROTONIN RE-UPTAKE
INHIBITORS
• A systematic review and meta-analysis of these trials showed that
SSRIs are effective in the treatment of PMS and PMDD.
• Women should be counselled about the possibility of sexual problems
including diminished libido, delayed orgasm and anorgasmia.
• Side effects are reduced by administering the lowest dose only during
the luteal phase of the cycle.
• Current evidence suggest that luteal phase treatment is as effective as
continuous therapy and is associated with fewer side effects.
• Example – Fluoxetine, Paroxetine, Citalopram

25. DIURETICS
• Research has suggested that spironolactone may be useful
for reducing abdominal bloating, swelling, mood symptoms
and breast discomfort. Its given during luteal phase.

26. NON-PHARMACEUTICAL DRUG BASED
TREATMENTS
• Herbal supplements: the only supplement that has been
reported as effective in albeit small placebo controlled trials
is Vitex agnus castus.
• Cognitive behavioural therapy: CBT has been shown to
effectively reduce premenstrual symptoms comparable to
treatment with fluoxetine over six months. Assessment after
12 months showed that the CBT effect may actually last
longer than the SSRI.
• Vitamin B6: A meta-analysis of vitamin B6 trials found it to
have a limited beneficial effect.
• Calcium: has been shown to be superior to placebo in some
RCTs.

27. TREATMENT - PREMENSTRUAL
EXACERBATION
• Treat either the underlying condition so that the
premenstrual phase can be tolerated by the patient or,
suppress ovulation using the previously mentioned
methods.

28. TREATMENT - PREMENSTRUAL DISORDER
WITH ABSENT MENSTRUATION
• Women who do not menstruate as a result of endometrial
ablation, hysterectomy or a levonorgestrel releasing
intrauterine system may still experience premenstrual
disorders.
• Treatment will be the same as with core premenstrual
disorder.

29. TREATMENT - PROGESTOGEN-INDUCED
PREMENSTRUAL DISORDER
• It is simple to rectify this by changing the dose, type,
duration or type of delivery, i.e. whether pill or
levonorgestrel releasing uterine device of the progestogen.

30. SUMMARY

31. SUMMARY

32. REFERENCES
• Obstetric & Gynaecology An Evidence Based Text for MRCOG 3rd
Edition
• Greentop Guidelines No. 48
• Stratog.rcog.org.uk