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Premenustrual Dysphoric Disorder and Post Menopausal Syndrome
Dr. Pavan Kumar.KAssistant Professor,Dept of Psychiatry
CAIMS
What is Premenstrual Dysphoric Disorder?
• PMDD• Severe PMS (Premenstrual
Syndrome)• Depression, tension and irritability
are common.
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
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’
PMDD is a relatively a new concept!
Our guide!1987DSM-III-R included criteria for Late Luteal Phase Dysphoric Disorder (in Appendix A, proposed diagnostics categories needing further studies)
1994In DSM-IV the name has been changed to Premenstrual Dysphoric DisorderIncluded as a Depressive Disorder Not Otherwise Specified (Appendix B, research criteria)
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).
PMDD - a Distinct Clinical Entity?
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
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.
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.
Risk Factors
• Anxiety• Major Depression• Seasonal affective disorder• Alcohol abuse• Overweight• Sedentary lifestyle• Family History
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).
markedly depressed mood, feelings of hopelessness, or self-deprecating thoughts
marked anxiety, tension, feelings of being "keyed up," or "on edge"
marked affective lability (e.g., feeling suddenly sad or tearful or increased sensitivity to rejection)
persistent and marked anger or irritability or increased interpersonal conflicts
(e.g. work, school, friends, hobbies)
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
In the most menstrual cycles during the past one year
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).
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).
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.
Diagnostic InstrumentsDRSP 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).
Symptoms
AnxietyDepressionIrritabilityLability of moodConcentration difficultySleep disturbanceFood cravings, overeatingAnhedonia
Breast tendernessBloatingBreast engorgementHeadachesMuscle or joint painWeight gain
ICD - 10
Requires only one physical or emotional symptom to make the diagnosis of PMS
ICD-10 does not include PMDD as a diagnosis
Differential Diagnosis
Premenstrual Syndrome
Premenstrual exacerbation of current mental disorder
Premenstrual exacerbation of general medical condition such as epilepsy, asthma or endocrine disorders
What goes wrong?
Common sense assumption
Assumption 1There might be a different hormone status in females with PMDD than those who do not have these symptoms
What goes wrong?
Common sense assumption
Assumption 2There might be serotonin depletion in PMDD, mainly in the luteal phase of menstruation!??
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)
Regular hormones levels
No consistent difference in blood and urine level of estrogen and progesterone in women with PMDD compared to those without disorder.
Why hormones involved?
If the fluctuation of hormones is somehow stopped,
the premenstrual symptoms improve!
GnRH agonists improves PMSSchmidt 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)
GnRH agonists improves PMS
Other supporting studiesFreeman 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.
Progesterone alone Used for many yearsNo 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
OC pills to suppress ovulation
Neurotransmitters
Retrospective evidence of Serotonin involvement- as the symptoms improves with SSRIs
SerotoninIncrease allopregnanolone synthesis
Increase sensitivity to neurosteroids
SSRIsThe effect is unrelated to the serotonin uptake inhibiting property of these drugs
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).
How can we go about helping her?
UpdateA 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).
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).
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).
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)
General nutritional recommendationLimit intake of alcohol, caffeine, salt, tobacco, and refined sugars
Increase complex carbohydrate and protein intake
Avoid overeating and weight gain
Consider frequent small meals
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)
Medication Treatment
SSRIsOther antidepressants
HormonesAnxiolyticsAnalgesicsDiureticsClonidineLithium
SSRIs
A thorough review of SSRIs by Dimmock and colleagues
Evaluated 15 high quality randomized placebo-controlled trials
(Lancet 2000;356:1131-1136)
SSRIsOverall, 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)
Very severe symptoms
Danazole
GnRH agonists
Surgical removal of ovaries
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)
POST MENOPAUSAL SYNDROME
• 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
• 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.
• 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
• 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.
• 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.
• 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.
• Vasomotor symptoms• Urogenital symptoms• Osteoporosis• Psychological problems
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.
• 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.
• These symptoms are managed by • Estrogen • Progesterone MPA (20mg/day)• Clonidine• SSRIS
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)
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.
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
Psychological symptoms
• Depression • Cognitve problems• Sleep problems
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.
• 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
Treatment
• SSRI• ESTROGEN • MPA
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.
Sleep disorders
• Insomnia occurs in 40-50% women during the menopausal transition.
• Age related???• Decrease in melatonin may be one of the
reason.
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