MAGDY ABDELRAHMAN MOHAMED 2015

PREMENSTRUAL TENTION SYNDROMES

PMS is a group of physical, mood-related, and behavioral changes that occur in a regular, cyclic relationship to the luteal phase of the menstrual cycle and interfere with some aspect of the patient’s life

PMDD identifies women with PMS who have more severe emotional symptoms (such as anger, irritability, and depression) that may require more extensive therapy

Definition

Severe (PMDD)

Moderate (PMS)

Mild (PMS)

None

Spectrum of Premenstrual Syndromes

PremenstrualSyndromeSeverity

Hacker & Moore: Hacker and Moore's Essentials of Obstetrics and Gynecology, 5th edition (2009), Neville F Hacker, Joseph C Gambone, Calvin J Hobel. Chapter 36 (387).

Premenstrual symptoms

Commonly seen in most of the females

Physiological

Not much distressful

No treatment or intervention generally sought

Premenstrual Syndrome (PMS)

Severe than commonly experienced physiological symptoms

Around 40% of females experience this cluster of various symptoms

However, impairment in daily functioning is less as compared to PMDD

Premenstrual Dysphoric Disorder (PMDD)

Severe form of PMS

Around 3% to 8% females experience it

Impairment in functioning:Work, Social interaction, Academics and even Daily Routine

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!

1987Diagnostic and Statistical Manual of Mental Disorders (DSM) -III-R included criteria for Late Luteal Phase Dysphoric Disorder.

1994In DSM-IV the name has been changed to Premenstrual Dysphoric DisorderIncluded as a Depressive Disorder Not Otherwise Specified.

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).

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

November 1999,US FDA Neuropharmacology Advisory Committee supported this concept

PMS/PMDD: Symptoms

Somatic Symptoms Breast tenderness Abdominal bloating – most common, occurs in 90% Headache Swelling of extremities Weight gain

Affective Symptoms Depression Angry outbursts Irritability Anxiety Confusion Social withdrawal Decreased concentration Sleep disturbance Appetite change/food cravings

PMS/PMDD: Symptoms

PMS/PMDD: Symptoms

Sample: Daily Symptoms Calendar

Diagnostic tool used to assist the patientwith recording her

premenstrual symptoms diary

Endicott and Harrison 2006. 5.Endicott, J., & Harrison, W. Daily Record of Severity of Problems Calendar .

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

Patient reports 1 affective symptom and somatic symptom(s) during the luteal phase before menses

Symptoms relieved within 4 days of onset of menses, without recurrence until at least cycle day 13

Symptoms occur in 2 consecutive menstrual cycles Patient suffers from identifiable dysfunction in social or

economic performance

PMS: Diagnosis

DSM-IV Criteria Symptoms interfere with usual functioning and relationships Symptoms are not an exacerbation of another disorder Symptoms resolve at onset of menses Premenstrual timing is confirmed by menstrual calendar in 2

consecutive cycles

PMDD: Diagnosis

DSM-IV Criteria At least 5 of 11 premenstrual symptoms

At least 1 of the following: Depressed mood Marked anxiety Marked affective lability Marked irritability

Other possible symptoms Decreased interest in regular activities Difficulty concentrating Lethargy/fatigue Appetite change/food cravings Sleep disturbance Feelings of being overwhelmed Physical symptoms (bloating, weight gain, breast tenderness, edema)

PMDD: Diagnosis

Differential Diagnosis

Premenstrual Syndrome.

Premenstrual exacerbation of current mental disorder.

Premenstrual exacerbation of general medical condition such as epilepsy, asthma or endocrine disorders.

Aetiology??? Ovarian hormones (sex steroids)

SerotoninOther neurotransmitter

Beta endorphinsAldosterone

ProlactinIons and minerals

OvariesLimbic system

Prefrontal cortexHippocampusHypothalamus

Pituitary?Kidney

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 PMS

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.

Allopregnanolone-a metabolite of progesterone

Summary of various reviews and studiesAllopregnanolone levels are high in PMDDIncrease in allopregnanolone in response to stress occur in PMDD

Allopregnanolone to progesterone ratio is higher in PMDD following an oral progesterone dose (Klatzkin et al. Psychoneuroendocrinology 2006;31:1208-1219)

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).

TREATMENT OPTIONS

Nutritional approaches

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)

Calcium

A large double blind placebo-controlled multi-center trial available

1200 mg daily

Effective in reducing PMS symptoms

Magnesium

Few placebo-controlled trials availabe

200 mg daily

Improves fluid retention problem

Evening primrose oil

little value even in PMS(Budeiri et al. Control Clin Trials 1996;17:60-68).

HerbsFemale Balance(a product widely sold on internet, containing unspecified amount of 16 herbs- as an effective, natural, gentle way for treating PMS)No scientific support

Hypericum perforatum (St. John’s Wart)Uncontrolled study available (small sample of 19 women)well designed controlled study needed(Stevinson and Ernst. BJOG 2000;107:870-876)

SSRIs Can be taken throughout the cycle or during the luteal phase

of the cycle Fluoxetine 20-60 mg qd

PMDD: Treatment (Medical)

Anti-depressants SSRI’s (Fluoxetine)

Spironolactone - bloating Bromocriptine – mastalgia Ovulation suppression

GnRH agonists (e.g. Lupron) Danazol OCPs

(Medical Treatment)

Oophorectomy Not generally recommended

Irreversible Reserved for severely affected patients who only respond to

GnRH agonists

PMS/PMDD: Treatment (Surgical)

Summary PMDD identifies women with PMS who have more severe

emotional symptoms that may require intensive therapy. The physiologic mechanism that results in the occurrence of

PMS and PMDD is not well understood. The diagnosis of PMS and PMDD is based on documentation of

the relationship of the patient’s symptoms to the luteal phase. DSM-IV criteria are used to establish the diagnosis of PMDD. In addition to lifestyle changes, behavioral therapies, and

dietary supplementation, some pharmacologic agents have been shown to have symptom relief.