dr anna fenton - gp cmegpcme.co.nz/pdf/2017 south/sat_room2_1100_fentonanna_pms.pdf · cyproterone...
TRANSCRIPT
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