Premenustrual dysphoric disorder and Post Menopausal Syndrome

1. Premenustrual Dysphoric Disorder
and Post Menopausal Syndrome
Dr. Pavan Kumar.K
Assistant Professor,
Dept of Psychiatry
CAIMS

2. What is Premenstrual Dysphoric
Disorder?
• PMDD
• Severe PMS (Premenstrual Syndrome)
• Depression, tension and irritability are
common.

3. Hippocrates (460-377 B.C.)
Described a group of conditions
that occurred prior to the onset of
menses,
in which women might develop
suicidal ideation and other severe
symptoms

4. Frank (in 1931)
Described 15 women experiencing
severe premenstrual symptoms
and coined the term ‘Premenstrual
Tension Syndrome
Green and Dalton (in 1953)
coined the term ‘Premenstrual
Syndrome’

5. PMDD is a relatively a new concept!

6. Our guide!
1987
DSM-III-R included criteria for Late Luteal Phase
Dysphoric Disorder (in Appendix A, proposed diagnostics
categories needing further studies)
1994
In DSM-IV the name has been changed to
Premenstrual Dysphoric Disorder
Included as a Depressive Disorder Not
Otherwise Specified (Appendix B, research criteria)

7. October 1998,
A panel of experts evaluated the evidence
then available, and a consensus was reached
that PMDD was a distinct clinical entity
A review by a group of experts "reached the consensus that
PMDD is a distinct entity with clinical and biological profiles
dissimilar to those seen with other disorders"
(Endicott et al. J Womens Health Gend Based Med
1999;8:663-679).

8. PMDD - a Distinct Clinical Entity?

9. A distinct clinical presentation with
characteristic symptoms
Cyclical course linked to the menstrual
cycle
Unique physical symptoms such as
bloating and breast tenderness
Cessation of symptoms during pregnancy
and after menopause
Rapid response to selective serotonin
reuptake inhibitors (SSRIs)—in contrast to
the slower onset in major depressive
disorder
Normal hypothalamic-pituitary-adrenal
axis functioning—in contrast to major
depression

10. Causes of PMDD
• The Causes are NOT KNOWN.
• Hormones play some sort of
role.
• Symptoms Disappear if
ovaries are removed.
• Ovarian function
may affect changes
in brain chemistry.

11. Incidence of PMDD
• Occurs in in 8% of woman who are having
their menstrual cycle.
• May have a genetic disposition.
• Daughters of mothers with PMDD are likely to
have the disorder as well.
• 93% of Identical twins will
both have PMDD.
• 44% of Fraternal twins will
both have PMDD.

12. Risk Factors
• Anxiety
• Major Depression
• Seasonal affective disorder
• Alcohol abuse
• Overweight
• Sedentary lifestyle
• Family History

13. In most menstrual cycles during the past 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
(1), (2), (3), or (4).

14. markedly depressed mood,
feelings of hopelessness,
or self-deprecating thoughts

15. marked anxiety,
tension,
feelings of being "keyed up," or "on
edge"

16. marked affective lability
(e.g., feeling suddenly sad or tearful or
increased sensitivity to rejection)

17. persistent and marked anger
or irritability
or increased interpersonal conflicts

18. (e.g. work, school, friends, hobbies)

19. Symptoms absent, the week after
the onset of menses (Follicular
Phase)
Symptoms subside few days
after the onset of menses
Symptoms present in the last
week of Luteal Phase

20. In the most menstrual cycles during the past one year

21. 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).

22. 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).

23. How to diagnose PMDD ?
• No physical exam or lab test can diagnose PMDD.
• Psychiatric evaluation is used to rule out other
conditions.
• Keep a calendar or diary of symptoms when they
occurred to help with a diagnosis and best course
of treatment.

24. Diagnostic Instruments
DRSP Daily Record of Severity of Problems
PSST Premenstrual Symptoms Screening
Tool
COPE Calendar of Premenstrual
Experiences
VAS Visual Analogue Scale
DSR Penn Daily Symptom Report Scale
The reliability and validity of the DRSP were confirmed
recently in two studies reported by Endicott et al. (Arch
Womens Ment Health 2006;9:41-49).

26. Symptoms
Anxiety
Depression
Irritability
Lability of mood
Concentration difficulty
Sleep disturbance
Food cravings, overeating
Anhedonia
Breast tenderness
Bloating
Breast engorgement
Headaches
Muscle or joint pain
Weight gain

28. ICD - 10
Requires only one physical or
emotional symptom to make the
diagnosis of PMS
ICD-10 does not include PMDD as a
diagnosis

29. Differential Diagnosis
Premenstrual Syndrome
Premenstrual exacerbation of current mental
disorder
Premenstrual exacerbation of general medical
condition such as epilepsy, asthma or
endocrine disorders

32. What goes wrong?
Common sense assumption
Assumption 1
There might be a different hormone status in
females with PMDD than those who do not
have these symptoms

33. What goes wrong?
Common sense assumption
Assumption 2
There might be serotonin depletion in PMDD,
mainly in the luteal phase of menstruation!??

34. What data has to say?
premenstrual syndrome is probably the result of
a complex interaction between
ovarian steroids
and
central neurotransmitters
(N Engl J Med 1998;338:256-257)

35. Regular hormones levels
No consistent difference in blood and urine
level of estrogen and progesterone in women
with PMDD compared to those without
disorder.

36. Why hormones involved?
If the fluctuation of hormones is somehow
stopped,
the premenstrual symptoms improve!

37. GnRH agonists improves PMS
Schmidt and colleagues
used leuprolide, a GnRH agonist,
to block endogenous production of estrogen and
progesterone in 10 women with PMS
conclusion:
 There was a significant decrease in PMS symptoms
compared to baseline and compared to a placebo group.
 This was followed by a marked worsening of PMS
symptoms when estrogen or progesterone was added to
leuprolide in the women who had benefited previously.
(N Engl J Med 1998;338:209-216)

38. GnRH agonists improves PMS
Other supporting studies
Freeman EW, Sondheitjer SH, Rickets K.
Gonadotropin-releasing hormone agonist in treatment of premenstrual
symptoms with and without ongoing dysphorics:
a controlled study. Psychopharmacol Bull. 1997;33:303-309
Hammarback S, Backstrom T.
Induced anovulation as treatment of premenstrual tension syndrome:
a double-blind cross-over study with GnRH-agonist versus placebo.
Acta Obstet Gynecol Scand. 1988;67:159-166.

39. Progesterone alone
Used for many years
No supporting evidence
Progesterone has not been demonstrated to work better
than placebo for treatment of mood symptoms of PMS.
-Ford O, Lethaby A, Mol B, Roberts H.
Progesterone for premenstrual syndrome.
Cochrane Database Syst Rev. 2006;(4):CD003415.
-Wyatt K, Dimmock P, Jones P, Obhrai M, O'Brien E.
Efficacy of progesterone and progestins in management of premenstrual symptoms: a
systematic review.
BMJ. 2001;323:776-780

40. OC pills to suppress ovulation

41. Neurotransmitters
Retrospective evidence of Serotonin involvement- as the
symptoms improves with SSRIs
Serotonin
Increase allopregnanolone synthesis
Increase sensitivity to neurosteroids
SSRIs
The effect is unrelated to the serotonin uptake inhibiting
property of these drugs

42. Genetic susceptibility
A preliminary study suggested that genetic
variation in the estrogen receptor alpha
gene is associated with increased risk for PMDD;
leading the authors to speculate that there might
be a "genetic susceptibility to affective
dysregulation induced by normal levels of
gonadal steroids"
(Huo et al. Biol Psychiatry 2007;62:925-933).

43. How can we go about helping her?

45. Update
A brief update on diagnosis and
treatment,
"Expert Guidelines for the Treatment
of Severe PMS, PMDD, and
Comorbidities: The Role of SSRIs“
published in 2006 by Steiner et al. (J Womens
Health (Larchmt) 2006;15:57-69).

46. Recent review
A more recent overview on treatment of
PMDD is provided by Yonkers and colleagues
(Lancet 2008;371:1200-1210).
The pharmacologic treatment of PMDD was
reviewed recently by Rapkin and Winer
(Expert Opin Pharmacother 2008;9:429-445)
and Steiner et al. (J Womens Health
2006;15:57-69).

48. CBT
Comparision with Fluoxetine and combination of
Fluoxetine and CBT
all three equally effective; though the response with
Fluoxetine faster
more sustained benefit from CBT after termination of
treatment
(Hunter et al. J Psychosom Obstet Gynecol 2002;23:193-199).

49. Nutritional approaches
Dietary modifications are recommended
widely to relieve symptoms of PMS, but
whether they are effective for treating the
more severe symptoms of PMDD has not been
established
Again more studies for PMS; so ?? For
severe symptoms of PMDD.
Limitations:
Poor study design, Vague definition of
PMS, High placebo response
(review by Bendich. J Am Coll Nutr 2000;19:3-12)

50. General nutritional recommendation
Limit intake of alcohol, caffeine, salt, tobacco, and
refined sugars
Increase complex carbohydrate and protein
intake
Avoid overeating and weight gain
Consider frequent small meals

51. Pyridoxine (vitamin B6)
Despite the limitation of study designs.
100 mg/day benefits in premenstrual
symptoms
by Wyatt et al.
(BMJ 1999;318:1375-1381)

52. Medication Treatment
SSRIs
Other antidepressants
Hormones
Anxiolytics
Analgesics
Diuretics
Clonidine
Lithium

53. SSRIs
A thorough review of SSRIs by Dimmock and
colleagues
Evaluated 15 high quality randomized
placebo-controlled trials
(Lancet 2000;356:1131-1136)

54. SSRIs
Overall, the SSRIs were 6.9 times more effective than
placebo.
With the exception of one negative study with
fluvoxamine, results with SSRIs for PMDD have been
uniformly positive
Drugs evaluated: Fluoxetine, Sertraline
Full cycle-more, few intermittent- same benefit
Unable to determine dose-response relationship
(Lancet 2000;356:1131-1136)

55. Very severe symptoms
Danazole
GnRH agonists
Surgical removal of ovaries

56. Treatment of PMDD
• A healthy lifestyle is the first step to managing
PMDD.
• Eat a Balanced Diet
• Get sufficient sleep
• Exercise
• Keep a track of your symptoms
• Other Treatments:
» Birth control Pills
» Diuretics
» Nutritional supplements
» Antidepressants
» CBT (Congenital behavioral Therapy)

57. POST MENOPAUSAL
SYNDROME

58. • The average age of menopause in India is
47.5years with an average life expectancy of
71years.
• So.., Indian women are likely to spend 23
years in menopause.
– Indian menopause Society, 2007

59. • Prakash and Murthy etal..
– A study done in 1981, observed the relationship
between menopause and psychiatric morbidity by
using GHQ, Psychiatric interview found highest
psychiatric morbidity in the menopausal group.

60. • Menopause is the permanent cessation of
menstruation resulting in the loss of ovarian
follicle development.
• Factors that are toxic to the ovary often result
in an earlier age of menopause.
• Premature ovarian failure is defined as
menopause before the age of 40 years

61. • Although menopause is associated with
changes in the hypothalamic and pituitary
hormones that regulate the menstrual cycle,
menopause is not a central event, but rather a
primary ovarian failure.

63. • Menopausal transition or perimenopause is a
defined period of time beginning with the onset
of irregular menstrual cycles until the last
menstrual period and is marked by fluctuation in
reproductive harmones.
• This period is characterised by menustrual
irregularities, prolonged and heavy
menustruation intermixed with episodes of
amenorrhea, decreased fertility, vasomotor
symptoms and insomnia.

64. • Menopause is defined retrospectively as the
time of the final menustrual period , followed
by 12months of amenorrhea.
• Post menopause describes the period
following the final menses.

66. • Vasomotor symptoms
• Urogenital symptoms
• Osteoporosis
• Psychological problems

67. VASOMOTOR SYMPTOMS
• Affects upto 75% of perimenopausal women.
• May last usually upto 1-2yrs but in some upto
10years.
• Hot Flushes
• Fatigue
• Should be differentiated from thyroid
abnormalities.

68. • Probably initiated in hypothalamus, which
drives an increased core body temperature,
metabolic rate and skin temperature, resulting
in peripheral vasodilatation and sweating.
• This may be triggered by 5HT, NE, DA
activation.

69. • These symptoms are managed by
• Estrogen
• Progesterone MPA (20mg/day)
• Clonidine
• SSRIS

70. ACOG updated Practice Bulletin- treating
vasomotor symptoms and vaginal atrophy-JAN
2014
• more evidence to support nonhormonal
alternatives (SSRI & SNRI) for management of
vasomotor symptoms.(paroxetine-only FDA
approved)
• transdermal delivery is safer than oral.(ACOG2013)

71. Urogenital atrophy
• Vaginal dryness, pruritis, dyspareunia, dysuria
and urgency.
• Treatment:
• These symptoms respond to estrogen therapy.
May be given orally/local application of
creams / vaginal suppository.

72. Osteoporosis
• Backache, fractures, decreased mobility are
common due to osteoporosis.
• Women should recieve 1000-1500 mg calcium
supplementation
• 400-800 IU of Vit D daily.
• HRT is effective in preventing and treating
osteoporosis.
• SERM : RAL0XIFEN 60MG
• BISPHOSPHONATES

73. Psychological symptoms
• Depression
• Cognitve problems
• Sleep problems

74. Depression
• Because of fluctuating and declining estrogen
levels in part.
• Steroid hormones like estrogens act by
stimulating the synthesis of
neurotransmitters, expression of receptors
and influence membrane permeability.
• Estrogen increases the effect of serotonin and
nor epinephrine which mediate mood.

75. • Alternate mechanism is estrogen decreases
MAO.
• Although precise mechanisms are not known,
fluctuations in estrogen levels affect the
regulation of serotonin and norepinephrine.
• LIFE STRESSORS
• EMPTY NEST SYNDROME
• LOSS OF FERTILITY

76. Treatment
• SSRI
• ESTROGEN
• MPA

77. COGNITIVE FUNCTIONS
• Memory problems are common in
menopausal transition rather than aging
process.
• Cognitive difficulties may be a consequence of
sleep disruptions secondary to nocturnal hot
flushes.
• Women are at greater risk for Alzheimer’s
disease than men.

78. Sleep disorders
• Insomnia occurs in 40-50% women during the
menopausal transition.
• Age related???
• Decrease in melatonin may be one of the
reason.

79. Cp5