Premenstrual syndrome management based on recent guidelines

1. Premenstrual
Syndrome – Recent
Guidelines
Dr Meenakshi Sharma
Consultant Obs & Gynae
Yashoda SuperspecialityHospital
Kaushambi

2. Premenstrual Syndrome & Premenstrual
Dysphoric Disorder
Incidence
80% of women have atleast one physical or psychiatric
symptom during luteal phase
 PMS -12-15%
 PMDD – 1.3-5.3%
AAFP 2016

3. Definition
 PMS -a condition in which a woman experiences at least
one affective symptom and one somatic symptom that
cause dysfunction in social, academic, or work
performance. These symptoms must be cyclical,
beginning after ovulation and resolving shortly after the
onset of menstruation
 PMDD -To meet the diagnostic criteria for PMDD, a
patient must have at least five of the symptoms in the
week before menses, and these symptoms must improve
within a few days after the onset of menses.

4. Breast tenderness
Headache
Abdominal bloatingAngry outbursts/ Anxiety
Depression

6. Classification of PMS (ISPMD consensus)
 Core premenstrual disorders (PMDs)
 Variant PMDs
 Premenstrual exacerbation of an underlying disorder
 Non-ovulatory PMDs
 Progestogen-induced PMDs
 PMDs with absent menstruation

7. Etiopathogenesis
 Sensitivity to progesterone and progestogens
 Neurotransmitters serotonin and c-aminobutyric acid
(GABA).

8. Treatment
Aim to relieve physical and psychiatric symptoms
 Suppression of Ovulation
 OCP
 GnRH
 Neurotransmitter modulation
 SSRI – sertaline, paroxetine, fluoxetine, citalopram, escitalopram
 SNRI -venlafaxine
 Complementary therapy
 Calcium & Vitamin D supplementation, Acupuncture
 Cognitive Behavior therapy

9. Clinical evidence of OCP in PMS
Little good quality evidence
Cyclical nature of PMS difficult to conduct RCT
Lack of consensus on PMS severity and scores

10. Cycle modifying agents in PMS
 COC
 Continuous versus cyclical
 LNG/Desogestrel/drospirenone
 Percutaneous Estradiol
 GnRH Agonist
RCOG, 2017

11. LNG/Norethisterone/Drospirenone COC
LNG or Norethisterone have PMS regenerating sideffects
A Cochrane review involving 5 RCTs and 1920 women,
Drospirenone COC Vs Placebo/other COC, concluded
that Drospirenone COC effectively reduces symptoms in
PMDD than placebo or other COC (mean difference 7.92; 95%
CI 11.16 to 4.67)
Cochrane , 2012
Drospirenone-containing COCs may represent effective
treatment for PMS and should be considered as a first-line
pharmaceutical intervention. B Evidence 1+
RCOG 2017

12. COC regimen – Continuous or Cyclical
 Comparative study of 168 day extended to 364 days
Drospirenone 3 mg and 20 mcg EE with 21/7 regimen
better symptom control with extended use
Coffee AL, AJOG, 2006
 COC to be used continuously rather than cyclically in
PMS. Evidence 2-
RCOG 2017

13. Percutaneous estradiol
 Percutaneous estradiol combined with cyclical
progestogens has been shown to be effective for the
management of physical and psychological symptoms of
severe PMS. A
 Lowest progestogen dose used, Micronised progesterone
preferred 10-12days/cycle
 Alternative barrier or IUCD should be used when estradiol
is used to suppress ovulation.
RCOG, 2017

14. GnRH in PMS
GnRH analogues are highly effective in treating
severe PMS. A
Reserved for severe PMS
Add back therapy (continuous combined HRT or
Tibolone) if use more than 6 months
Screen for osteoporosis with long term use with
BMD every year
RCOG, 2017

15. SSRI in PMS
 Cochrane review of 31 RCT comparing SSRI with placebo
concluded that symptoms improved with SSRI as
compared to placebo.
Cochrane 2013
 SSRIs should be considered as one of the first-line
pharmaceutical management options in severe PMS. A
 Both luteal or continuous dosing with SSRIs can be
recommended. B
 SSRI - Fluoxetine, paroxetine, sertraline, escitalopram and
citalopram
 SNRI venlafaxine is also beneficial in PMDD
RCOG 2017

16. SSRI in PMS
 SSRIs should be discontinued gradually to avoid
withdrawal symptoms, if given on a continuous basis
 Adverse effects - nausea, insomnia, somnolence, fatigue
and reduction in libido
 Side effects minimised with luteal phase or symptom
onset regimen using new agents eg Citalopram,
escitalopram
 SSRI should be stopped prior to conception due to
possible teratogenicity

17. Complementary therapy in PMS
RCOG, 2017
Complementary
therapy
Benefit Type of studies (no of
published studies)
Note
Exercise Some
benefit
Nonrandomised and
randomised (4)
Vitamin B6 Mixed
result
Double blind RCT crossover
(13)
Peripheral neuropathy in high
doses
Calcium Vitamin
D
Yes Double-blind Randomised
Cross-over (2)
Vitex agnus
castus
yes Double blind RCT (7) No standard preparation
available
Isoflavones Mixed
result
Double-blind Randomised
Cross-over (2)
Benefit in menstrual migraine
Evening
primrose
oil
Mixed
result
Double-blind placebo
controlled Cross-over, (4)
Benefit in cyclical mastalgia
Acupuncture Some
benefit
Case control (10) High bias

18. Cognitive behaviour therapy
 CBT should be considered routinely as a treatment option
in severe PMS A
 Significant reduction in depression, anxiety and
behavioural problems.- avoid pharmacotherapy and
potential adverse effects
RCOG, 2017

19. Surgical therapy in PMS – Is it justified?
 In severe PMS, hysterectomy and bilateral oophorectomy has been
shown to be of benefit. D
 Indicated only in selected severe refractory case
 Unsuccessful medical management
 Long-term GnRH analogue treatment
 Gynaecological co morbidities indicate hysterectomy
 In women less than 45 years prior Rx with GnRH as test of care can
be done with HRT for its tolerance
 Endometrial ablation and hysterectomy with conservation of the
ovaries are not recommended.
 Bilateral oopherectomy alone not recommended as subsequent HRT
with progestin regenerate PMD like illness

21. Case 1
 A 22 year P1L1 lady presents with abdominal boating with
some feeling of lack of energy, lethargy and depressive
thoughts occurring in a week prior to menstruation.
 Symptoms resolves after 3 days of onset of menstruation
 Symptoms do not interfere with her day to day activities
 She is concerned of some underlying disease
What is the diagnosis?
How will you treat?

22.  Diagnosis - Physiological Premenstrual Disorder
 Reassurance
 No Pharmacological treatment required
 If patient desires COC for contraception, Drospirenone
COC preferred

23. Case 2
 A 45 year old P2L2 lady is on Treatment for DUB. She is
taking Norethisterone 10 mg daily for last 3 months.
 C/o abdominal bloating,
 Weight gain
 Depressive mood
 for last 3 months 2 weeks in a month which gets relieved
with onset of menstruation.
 M/H regular cycles on treatment with average flow.
What is the diagnosis?

24.  Progestogen induced PMD
 Alternative Progesterone to be used. LNG IUS may be
offered

25. 25

26. Continuous combined OCP
 One systemic review (no RCT included) and 1 RCT in women
with PMDD
 RCT 386 women with PMDD compared Continuous combined
OCP (90mcg LNG and 20 mcg EE) to placebo for 112 days (4
cycles)
 Significant improvement of symptoms in OCP group at one
month but no difference at three months
 Averse effect metrorrhagia, flu syndrome, and DVT more
common in OCP group
Lopez LM, Kaptein A, Cochrane 2011
Halbreich U, Contraception, 2012
 No RCT comparing continuous combined OCP versus
cyclical combined OCP in PMS /PMDD

27. Continuous Transdermal Estradiol in
women with intact uterus in PMS
 One crossover double blind RCT, (n-40)continuous transdermal
estradiol compared with placebo with oral norethistrone from
day 19-26 of each cycle for 6 month with crossover at 3 month
 Improvement in symptom at 3 month in both groups, after
crossover scores deteriorate in women switching from active
treatment to placebo while scores keep improving in women
switch over from placebo to active treatment
 Adverse effect were mild skin irritation and pigmentation
Watson NR, Lancet 1989

28. Continuous subcutaneous Estradiol
implant in PMS
 One double blind RCT (68 women) compared
subcutaneous estradiol with placebo implant, with oral
norethisterone for 7 days per cycle both groups
 Estradiol implant more effective than placebo up to 6
month
 Adverse effect mild headache and weight gain
Magos AL, BMJ, 1986

29. Guidelines for treating PMS - RCOG 2017
 When treating women with severe PMS, CBT should be
considered routinely as a treatment option. A
 When treating women with PMS, drospirenone-containing
COCs may represent effective treatment for PMS and
should be considered as a first-line pharmaceutical
intervention. [New 2016] B
 When treating women with PMS, emerging data suggest
use of the contraceptive pill continuously rather than
cyclically.

30. Guidelines for treating PMS - RCOG 2017
 Percutaneous estradiol combined with cyclical
progestogens has been shown to be effective for the
management of physical and psychological symptoms of
severe PMS. A
 Lowest possible dose of progesterone or progestogen is
recommended to minimise progestogenic adverse
effects. [New 2016]A
 Micronised progesterone is theoretically less likely to
reintroduce PMS-like symptoms and should therefore be
considered as first line for progestogenic opposition
rather than progestogens. [New 2016]

31. Guidelines for treating PMS - RCOG 2017
 When treating women with percutaneous estradiol, a
cyclical 10–12 day course of oral or vaginal progesterone
or long-term progestogen with the LNG-IUS 52 mg should
be used for the prevention of endometrial hyperplasia. [
 GnRH analogues are highly effective in treating severe
PMS. [New 2016] A
 When treating women with PMS, GnRH analogues should
usually be reserved for women with the most severe
symptoms and not recommended routinely unless they
are being used to aid diagnosis or treat particularly
severe cases.

32. Guidelines for treating PMS - RCOG 2017
 SSRIs (luteal or continuous) should be considered one of the first-line
pharmaceutical management options in severe PMS. [New 2016] A
 When treating women with PMS, surgery should not be
contemplated without preoperative use of GnRH analogues as a
test of cure and to ensure that HRT is tolerated.
 When treating women with severe PMS, endometrial ablation and
hysterectomy with conservation of the ovaries are not
recommended. [New 2016]
 Bilateral oophorectomy alone (without removal of the uterus) will
necessitate the use of a progestogen as part of any subsequent HRT
regimen and this carries a risk of reintroduction of PMS-like symptoms
(progestogen-induced premenstrual disorder). [New 2016]