Dr Anna FentonGynaecological Endocrinologist

Christchurch

11:00 - 11:55 WS #89: Pre Menstrual Syndrome - PMS - Is It All in the Head?

12:05 - 13:00 WS #100: Pre Menstrual Syndrome - PMS - Is It All in the Head?

(Repeated)

PMS:

Is it all in the head?

Yes and No!Dr Anna Fenton

Endocrinologist CDHB and Women’s Health @ Southern Cross

BHB MBChB CCD PhD FRACP

Disclosures

• AdvisoryBoardPfizer

• PTACEndocrinesub-committee

Premenstrual syndrome

Which of the following is correct?

Women with PMS usually have abnormal ovarian hormones

PMDD affects 2-4% of reproductive age women

PMS gets better as women approach menopause

Abnormal serotonin metabolism is an important contributor to

PMS

Progesterone treatment is an effective way to manage PMS

Premenstrual syndrome

Which of the following is correct?

Women with PMS usually have abnormal ovarian hormones ✖️

PMDD affects 2-4% of reproductive age women ✖️

PMS gets better as women approach menopause ✖️

Abnormal serotonin metabolism is an important contributor to

PMS ✔️

Progesterone treatment is an effective way to manage PMS ✖️

GnRH

Inhibin

Pituitary

Gonadotropins:

- LH, FSH

Steroids

Hypothalamus

Feedback

hormones

Hypothalamic-pituitary ovarian axis

Ovary

Hormone levels over a normal

menstrual cycle

Testosterone levels over the menstrual

cycle

Estrogen, progesterone and

neurotransmitters

Estrogen regulates the activity and synthesis of serotonin and

acetylcholine

It interacts with noradrenaline and dopamine

Estrogen generally lifts mood

Progesterone, via a metabolite, alters the GABA system and

enhances MAO activity. The latter decreases noradrenaline,

dopamine and serotonin

Progestogens may lower mood and enhance sedation

Mood and the menstrual cycle

Individual vulnerability to normal hormone changes lead to:

PMS/PMDD

Post -natal depression

Menopause related mood changes, anxiety and psychosis

It is often the change in hormone levels rather than the absolute

level that is the problem

It may be the same women who present with recurrent hormone -

related mood issues at different stages of their reproductive lives.

Hormone levels over a normal

menstrual cycle

Menstrual mood disorders

PMS/PMDD becomes more common with age, particularly after 35yrs of age

It is triggered by hormone swings mid -cycle and pre-period

A cascade of changes in neurotransmitters and other hormones

(androgens, mineralocorticoids) then occur and cause both physical and psychological sx.

If PMS presents at or before 30yrs there is often an underlying hormone disorder driving this. This is often polycystic ovary syndrome

BMI > 30 increases the risk 3-fold

Smoking increases the risk 2-fold

Family hx of depression, sexual or domestic abuse are risk factors

Premenstrual Syndrome

Up to 90% of reproductive age women report sx of PMS

20% experience PMS

3-8% have sx that meet the criteria for PMDD.

Women with PMDD have a 50-75% lifetime incidence of psychiatric

disorders

Mutations in the estrogen receptor have been detected in women

with PMDD

The average woman has usually seen multiple doctors over a

period of years before the diagnosis is made

Sx begin after ovulation and resolve early in the menstrual cycle.

There is always a clear window without sx during the later follicular

phase of the cycle

The pattern is consistent over 2-3 cycles

Huo et al., Biol Psychiatry. 2007;62(8):925-33

Premenstrual Syndrome

A complex disorder

Is driven by ovulation

Abnormalities described in estrogen, androgen, prolactin

and mineralocorticoid production and action

Premenstrual Syndrome

This is a diagnosis made by taking a history

Collect data over at least 2 cycles

There should be a phase during the late follicular phase of complete

“normality”

There are no specific diagnostic tests or imaging

Rule out contributing disorders

PMS Symptom Rating Scale

Premenstrual Syndrome

We make a diagnosis of PMS if a woman has:

One to four symptoms that may be physical, behavioral,

or affective/psychological in nature, or

≥5 symptoms that are physical or behavioral.

If, on the other hand, a woman has ≥5 symptoms and one of them is an

"affective symptom" (eg, mood swings, anger, irritability, sense of

hopelessness or tension, anxiety or feeling on edge), it is more accurate

to diagnose her with PMDD rather than PMS.

DSM-5 Criteria for PMDD

One or more of the following symptoms must be present:

Mood swings, sudden sadness, increased sensitivity to rejection

Anger , irritability

Sense of hopelessness, depressed mood, self-critical thoughts

Tension , anxiety, feeling on edge

One or more of the following symptoms must be present to reach a total of five symptoms

overall:

Difficulty concentrating

Change in appetite, food cravings, overeating

Diminished interest in usual activities

Easy fatigability, decreased energy

Feeling overwhelmed, or out of control

Breast tenderness, bloating, weight gain, or joint/muscles aches

Sleeping too much or not sleeping enough

Differential Diagnosis

Mood and anxiety disorders

Menopause

Thyroid disease

Substance abuse

Menstrual mood disorders

Modulating hormone swings has a significant impact on menstrual

mood disorders

Simple treatment options include:

Diet/lifestyle/alcohol

Relaxation, CBT, light therapy, massage

CAMS: Vitex Agnus castus 20-40mg/day, saffron

Calcium/magnesium

Low ionized calcium in women with PMDD

Good data with calcium supplements. Less robust data with

magnesium – thought to act via changes in dopamine

Rx: 1000mg calcium; 600mg magnesium

Menstrual mood disorders

The contraceptive pill

In general, doesn’t work as it does not abolish the background hormone swings

Yaz

Anti-androgen and anti-mineralocorticoid

Spironolactone

Anti-androgen and anti-mineralocorticoid. Improves mood and physical sx.

High dose transdermal estrogen

Low quality data

Problems with addition of the progestogen

Cyproterone

Anti-androgen and anti-gonadotrophic

Menstrual mood disorders

SSRIs

Rapid onset of action suggests effect may be largely due to hormone modulation

Can be used for the luteal phase only.

Paroxetine and sertraline best studied. Citalopram and escitalopram also effective.

No strong predictors of response

LrH analogues (Zoladex)

Create a medically-induced menopause

Estrogen/progestogen add -back required if used in the longer term. This can be problematic

Bilateral oophorectomy with hysterectomy

Cochrane database 2013

Menstrual mood disorders

SSRIs

Rapid onset of action suggests effect may be largely due to hormone modulation

Can be used for the luteal phase only.

Paroxetine and sertraline best studied. Citalopram and escitalopram also effective.

No strong predictors of response

LrH analogues (Zoladex)

Create a medically-induced menopause

Estrogen/progestogen add-back required if used in the longer term. This can be problematic

Bilateral oophorectomy with hysterectomy

A study of hormone

modulation

Cyproterone + Progynova

Cyproterone acetate acts as an anti-androgen and anti-

gonadotropin

It suppresses hormone swings and ovulation to a greater degree

than the OCP

It is combined with estradiol to maintain stable estrogen levels

Fenton et al., 2017 submitted

Design

Prospective study of women starting cyproterone acetate for

treatment resistant menstrual disorders at Christchurch

Women’s Hospital and Southern Cross Hospital, Christchurch.

Women with active liver disease, a history of VTE or those

lacking capacity to give informed consent were excluded

Cyproterone 50mg daily + estradiol 2mg/50ug were

prescribed after a comprehensive history and examination

and baseline blood tests

The women were reviewed after 3mths of therapy. Clinical

examination and blood tests were repeated. Doses were

adjusted as required

All women gave informed consent

The data is shown for 470 consecutive women seen between

2008 and 2015

Medical Diagnoses

0

50

100

150

200

250

Number of

women

Average age

0

10

20

30

40

50

60

Age

(yrs)

Response to therapy

0

20

40

60

80

100

Improvement in

sx

Worsening of sx No change

% R

esp

on

se

Summary

PMS/PMDD is associated with a significant impact on quality

of life for the woman, her family and her workplace

It is common

It can be treated

There are a range of effective options for women and the

choice will depend in part on the severity of the PMS/PMDD