Premenstrual Dysphoric Disorder (PMDD) – Flashcards
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Past Questions:
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(2015) Discuss evidence for the inclusion of premenstrual dysphoric disorder in the DSM (2015) Should the NHS invest in both pharmacological and non-pharmacological treatments of premenstrual dysphoric disorder?
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Premenstrual Dysphoric Disorder (PMDD)
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- PMDD is a specific mental problem for certain women of reproductive age - It has a unique set of criteria and distinct set of symptoms - This results in a difficulty to diagnose - As a result, people are often misdiagnosed
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The Menstrual Cycle
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- The MC starts from the first day blood starts leaving the vagina - The entire duration can be divided into four main phases: 1) Menstural Phase 2) Follicular Phase 3) Ovulation Phase 4) Luteal Phase
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1) Menstural Phase
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- Days 1-5 - The uterus sheds its inner lining of soft tissue and blood vessels that exist in the body from the vagina in the form of menstural fluid - A blood loss of 10-80ml is considered normal -
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2) Follicular Phase
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- Days 1-13 - The pituitary gland secretes follicle stimulating hormone (FSH) that stimulates the egg cells in the ovaries to grow - One of these egg cells begins to mature in a sac-like-structure called follicle - It takes 13 days for the egg to reach maturity - While the egg cell matures, its follicle secretes a hormone that stimulates the uterus to develop a lining of blood vessels and soft tissue called endometrium
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3) Ovulation Phase
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- Day 14 - The pituitary gland secretes the production of luteinzing hormone (LH) which causes the ovary to release the matured egg cell - The release egg call is swept into the fallopian tube by the cilia of the fimbriae
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4) Luteal Phase
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- Days 15-28 - This phase lasts until the end of the cycle - During the luteal phase, the pituitary hormones FSH and LH cause the remaining parts of the dominant follicle to transform into the corpus luteum, which produces progesterone - The increased progesterone in the adrenals starts to induce the production of estrogen
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Problems with the Menstrual Cycle
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- Premenstrual symptoms only occur during the second half of the cycle - For some women, they have only mild symptoms which don't stop them doing anything - For others it can be incredibly disruptive to their every day life - 85% of mensturating women have reported at least one premenstrual symptom (ACOG, 2000) - If sufficient enough to interfere with some aspect of the women's life, then it may be considered as PMS
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Premenstrual Syndrome (PMS)
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- To be diagnosed with PMS women must experience at least one affective and one somatic symptom which disrupts their life in some significant way: > Affective symptoms = anger, anxiety, social withdrawal, confusion depression, irritability > Somatic symptom = headache, tender/swollen/painful breasts, water retention/extremities swelling/abdomen bloating - Additional diagnostic criteria must be present to confirm PMS diagnosis by a health professional - PMDD is ultimately an extreme version of PMS with many more symptoms - It has has only recently been acknowledged
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HISTORY OF PMDD:
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- The awareness that there are difficulties at the time surrounding menstruation has been around for centuries
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- Pre-1800's
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- Hippocrates described observed premenstrual mood changes as 'releasing bad humours' - An 11th century gynecologist, named Ttotula of Salerno, commented in a book 'The Disease of Women' states "There are young women who are relieved when the menses are called forth'
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- 1847
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- A description of menses moodiness by Dr Ernst F. Von Feuchtersleben
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- 1931
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- Term "Premenstrual Tension" was coined by American neurologist Dr Robert Frank
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- 1938
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- Dr Leon Israel was the first obstetric gynecologist specialist to use the term Premenstrual Tension - He quantified the time of the menstrual cycle that mood changes and symptoms occur
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- 1953
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- The term 'Premenstrual Syndrome' was coined by British Dr Katharina Dalton - She established the first clinic to treat the condition in Britain
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- 1982
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- The National Institute of Mental Health provided research criteria for studying PMS - Recommended prospective symptoms reporting and symptom severity determination
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- 1987
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- Gradually the term became more recognised - APA distinguished Late Luteal Phase Dysphoric Disorder (LLPDD) as a severe form of PMS - However, it was only quoted in the appendix of the DSM-3 - Prior to this, PMS was recognised, but PMDD was not
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- 1994
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- The name eventually changed to PMDD in the DSM-4, however, it was still in the appendix
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- 2013
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- Finally, in 2013, after lengthy discussions and much research, it was deemed that there was sufficient evidence for PMDD - PMDD moved into the main body of the DSM-5 under the section of depressive disorders - It was finally recognised as a diagnosed disease - It was found across all cultures and specific differences were seen in women who had PMDD compared to those who did not - The found consistency in the regularity of patterns showing how it can be predicted
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DIAGNOSING PMDD:
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1) DSM-5 2) Tools
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1) DSM-5 - Current diagnostic criteria for PMDD
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- The diagnosis of PMDD requires at least five of the 11 specific premenstrual symptoms including one of the core mood symptoms (marked depression, anxiety or tension, mood swings or persistent anger and irritability) - Other symptoms include decreased interest in activities, fatigue, marked changes in appetite, sleep disturbance, overwhelming feelings, physical symptoms - The symptoms must interfere with work, school, social life etc. - The symptoms must not be the result of anything else (e.g. drugs or another disorder) - These symptoms should be confirmed for at least two consecutive cycles - The symptoms occur one week before the period and carry on for a few days once it has started
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2) Tools for the diagnosis of PMDD
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- PMDD requires a consistent pattern of psychological, physical and/or behavioural systems during the luteal phase that ceases during menses - This is different from regular depression because it follows a cyclical pattern of onset - Measuring this can be done in various ways - Essentially, one needs to show the consistency and severity of their illness
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Tool 1: Daily Record of Severity of Problems (Endicott and Harrison, 2006)
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- One of the most popular prospective tools
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Tool 2: Premenstrual Symptoms Screening Tool (Steiner et al, 2003)
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- One of the most popular retrospective tools - It has been shown to be a good effective screener
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Tool 3: Rapkin and Lewis (2013)
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- Suggest patients developing own measures with scoring keys
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Diagnosis continued
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- There should also be a thorough medical history and physical examination undertaken in order to rule out any other underlying causes for the symptoms - e.g. other medical conditions that may flare during a premenstrual phase, such as IBS, chronic fatigue syndrome, anemia etc (Rapkin and Mikacich, 2013) - Incidence of domestic violence, physical and emotional trauma, or substance abuse, must be considered as may be related to PMS/PMDD (Perkonigg et al, 2004)
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Screening
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- Psychiatric illness screening is important if history raises other possible conditions, or ratings highlight that PM phase may be exacerbating an underlying condition (e.g seasonal affective disorder, generalised anxiety disorder etc.) or if there is suicide ideation - Family history of major depression and postpartum depression can also be risk factors to consider (Bancroft et al, 1994)
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Misdiagnosis:
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- Unfortunately, there are many negative accounts of women being diagnosed with PMDD - Evidence of misdiagnosis have been recorded e.g. bipolar (Studd, 2012) or borderline personality disorder (Yamauchi et al, 2008) - Kraemer et al (1998) found women sought help for many years before diagnosis, with PMDD suggestion often from a non-medical source - Consequently, women often felt physicians inadequately informed
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Progress
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- There is still a long way to go - Recent evidence suggests women as still having to 'fight' to receive a proper treatment and diagnosis - There is a general lack of awareness by GP's - There certainly seems to remain a lack of understanding of what the path is and what needs to happen - There is no simple test to say yes or no - There are other issues with getting the prevalence rates correct because we don't really know why the disorder happens
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EPIDEMIOLOGY FOR PMDD:
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- A total of 20-30% of women may be affected by moderate-to-severe symptoms that meet criteria for PMS - 3-8% will also fulfill the strict criteria for PMDD (Halbriech, 2003)] - The prevalence is universal and not bound to country or culture (Hong et al, 2012) - Surprisingly, one study found that up to 18% of women lacked only one of the requisite symptoms for a PMDD classification, indicating that many women are 'near threshold' for the diagnosis (Wichen et al, 2002) - However, these figures are questioned with regards to the methodoly used - Many argue they are an underestimation
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THEORIES OF PMDD:
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1) Ovarian Hormone Hypothesis 2) Serotonin Hypothesis 3) Psychosocial Hypothesis 4) Cognitive and Social Learning Theory 5) Sociocultural Theory
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1) Ovarian Hormone Hypothesis
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- Suggests that PMDD is caused by an imbalance in the estrogen-to-progesterone ration, with a relative progesterone deficiency - Accordingly, in the 1960's, patients were treated with progesterone suppositories - However, the research on this was inconsistent and inconclusive, mainly because of methodological differences - The current understanding seems to be that normal hormonal fluctuation trigger central biochemical events related to PMDD symptoms in some predisposed women
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2) The Serotonin Hormone Hypothesis
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- Hypothesises that normal ovarian hormone function (rather than hormone imbalance) is the cyclical trigger for PMDD-related biochemical events within the CNS and other target issues - It believes that there is a dysregulation of serotonin in the body - Research is starting to build up a nice body of evidence showing that serotonin is showing a role in PMDD - Essentially, hypothesised that women with PMDD have a particular sensitivity during these disturbances
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3) Psychosocial Theory
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- PMDD or PMS is a consious manifestation of a women's unconscious conflict about femininity and motherhood - Psychoanalysts proposed that premenstrual physical changes reminded the woman that she was not pregnant and therefore was not fulfilling her traditional feminine role - Obviously, proving this theory through scientific evidence is quite difficult
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4) Cognitive and Social Learning Theory
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- Hypothesise that the onset of menses is an aversive psychological event for women susceptible to PMDD - Moreover, these women might have had negative and extreme thoughts that further reinforce the aversiveness of premenstrual symptoms - Consequently, these women develop maladaptive coping strategies (eg, lability of mood, absence from school or work, and overeating) in an attempt to reduce the immediate stress - The immediate reduction of stress acts as a reinforcement, leading to the regular recurrence of symptoms during the premenstrual period
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5) Socio-cultural Theory
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- Believes that PMDD is a manifestation of the conflict between the dual roles society expects women to fill simultaneously—namely, productive workers and child-rearing mothers - PMDD is postulated to be a cultural expression of women's discontent with the traditional role of women in the society
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Summary of theories:
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- Of these 5 theories, the serotonin theory is perhaps the most popular at present - Although genetic predisposition and societal expectations may play a role, the strongest scientific data implicate serotonin as the primary neurotransmitter whose levels are affected by ovarian steroid levels - Other neurotransmitter systems that have been implicated include the opioid, adrenergic, and gamma-aminobutyric acid (GABA) systems
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TREATMENT OF PMDD:
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- Various forms of treatment have been attempted to treat PMDD, some with success and some without - On the whole, PMDD is majorly under-researched and unsurprisingly most of the research is done from pharmacological companies because they have the money - Some of the main areas of treatment can be split into: 1) Pharmacological Therapies 2)
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1) Pharmacological Therapies
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a) Hormones b) Diuretics c) Nonsterodial anti-inflammatory drugs d) Beta-blockers e) Antidepressants f) Anticonvulsants
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a) Hormones
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- Hormonal therapy attempts to suppress hypothalamic-pituitary-gonadal axis and control sex steroid fluctuations in lutual phase (i.e. stop ovulation) - Oral contraceptives - the results have been inconsistent in alleviating symptoms - However, some particular promise with Drospirenone-containing OC's found to relieve symptoms, and improve loss of productivity and impairment of social relationships
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b) Diuretics
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- Diuretics are used widely, under the assumption that many symptoms of PMS are secondary to fluid retention - Five randomized control trials that used spironolactone reported an improvement in premenstrual symptoms compared with placebo (Wyatt et al, 2000) - In 1976, Werch and Kane reported the beneficial effect of metolazone - Adverse effects include nausea, dizziness, palpitations, excess diuresis, and weakness.
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c) Nonsterodial anti-inflammatory drugs
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- Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used - In 5 randomized, controlled trials, mefenamic acid yielded greater improvement of premenstrual symptoms (except breast pain) than placebo (Wyatt et al, 2000) - In a placebo-controlled trial, naproxen sodium was more effective than placebo for physical symptoms - Another trial reported significant improvement in mood changes and headache with naproxen sodium as compared with placebo - Adverse effects include nausea, vomiting, epigastric pain, gastrointestinal (GI) bleeding, and rash
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d) Beta-blockers
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- Two trials of BB's have found favorable effects
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e) Antidepressants
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- The serotonergic system has a close relationship with the gonadal hormones and thus has been identified as the most plausible target for intervention - Selective serotonin reuptake inhibitors (SSRIs) are emerging as the most effective treatment option for PMDD - Of these agents, fluoxetine, sertraline, and controlled-release paroxetine have been approved by the US Food and Drug Administration (FDA) for treatment of PMDD
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Rapkin and Lewis (2013)
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- SSRI's are considered to be effective treatments as they can alleviate symptoms in over 60-80% of patients - Patients can experience a 50% reduction in PMDD symptoms
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f) Anticonvulsants
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- Kindling and impaired electroencephalophysiology have been suggested to play a role in the pathophysiology of PMDD - Levetiracetam is a novel antiepileptic drug that has shown strong antikindling activity in animal models of epilepsy - In a pilot open-label study, 6 of 7 patients experienced a considerable decrease in their Daily Record of Severity of Problems scores with levetiracetam, starting from the first treatment cycle (Kayatekin et al, 2008) - This suggests that anticonvulsant medications, specifically levetiracetam, could be effective in the treatment of PMDD
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2) Non-pharmacological Therapy
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a) Acupuncture b) Relaxation techniques c) Light Therapy d) Sleep Deprivation e) Cognitive-Behavioural Therapy
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a) Acupuncture
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- In a systematic review of 10 trials with methodologic limitations comparing acupuncture versus sham acupuncture, medication, or no treatment for premenstrual syndrome, acupuncture was associated with improved symptoms compared with any control in an analysis of 8 trials with 429 patients (Kim et al, 2011) - However, important methodological limitations in the included trials weakened the evidence
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b) Relaxation techniques
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- The relaxation response is a physiologic response that results in decreased metabolism, a lower heart rate, reduced blood pressure, a lower rate of breathing, and slower brain waves - The repetition of a word, sound, prayer, phrase, or muscular activity is required to elicit the relaxation response - Most studies of relaxation techniques have used them as adjuncts to other modalities of therapy - Available trials of relaxation treatment showed conflicting results. In one study, twice-daily relaxation therapy yielded greater improvement in physical symptoms of PMDD than keeping a daily symptoms chart and leisure reading (Goodale et al, 1990) - In another study, relaxation therapy was less effective than coping skills training
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c) Light Therapy
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- The basis of light therapy is replacing conventional lamps with full-spectrum fluorescent lamps whose light (referred to as bright light) is more similar to sunlight - The effect of bright light was postulated to be mediated through the serotonin system - Krasnick et al (2005) carried out a systematic review of 4 RCT's looking at bright light therapy for PMDD in 55 subjects - All 4 trials reported that BLT was effective in reducing depressive symptoms - However, it was concluded that numerous methodological issues did not permit definitive conclusions regarding the impact of BLT on PMDD
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d) Sleep Deprivation
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- Due to the similarities in PMDD and major depressive disorders, some of the treatments are thought to work for both - A randomized crossover trial comparing early-night sleep deprivation with late-night sleep deprivation in research subjects with PMDD found that both early and late sleep deprivation significantly reduced depressive symptoms after a night of recovery sleep but not after a night of sleep deprivation - The healthy comparison subjects showed no clinically important mood changes. The efficacy of sleep deprivation in reducing depressive symptoms in PMDD parallels its efficacy in major depressive disorder (Parry, 1995)
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e) Cognitive-Behavioural Therapy
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- CBT based on the view that behavioral disorders are influenced by negative or extreme thought patterns, which are so habitual that they become automatic and are unnoticed by the individual - Cognitive treatment teaches patients ways of examining these negative patterns and replacing them with more adaptive ways of viewing life events. CBT for PMDD includes anger control, thought stopping, and reduction of negative emotions through cognitive restructuring - Results of the effectiveness of CBT are not consistent
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3) Alternative Therapies
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a) Diet b) Hysterectomy c) Activity d) Nutritional and Herbal Formulations
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a) Diet
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- Dietary advice constitutes and important aspect of non-pharmacological treatment of PMDD - Reducing caffeine intake can reduce nervousness and jitteriness - Restricting sodium intake may reduce bloating - Consumption of complex carbohydrates and restrictioj or moderation of caffeine and alcohol intake have not been consistently beneficial in alleviating the symptoms of PMDD - One trial found evidence for reduction in symptoms from a low-fat vegetarian diet
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b) Hysterectomy and Ophorectomy
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- Also known as surgical menopause - This involves the removal of the uterus and removal of the ovaries - This causes women to go into early menopause - As a result they need to take other supplementary hormones
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c) Activity
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- Three randomized controlled trials reported that moderate aerobic exercise improved premenstrual symptoms - Traditionally, aerobic exercise is recommended, particularly if depressive or fluid retention symptoms predominate. From the available scientific data, it is unclear whether aerobic exercise is more effective than non-aerobic exercise - The efficacy of exercise could be the result of raised endorphin levels, physiologic changes, psychological changes, or combinations thereof
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d) Nutritional and Herbal Formulations
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- Nutritional supplements often used by women in self-treatment of PMS symptoms include the following: Vitamin B complex Calcium with magnesium chloride Evening primrose oil - Herbal formulations often used by women in self-treatment of PMS symptoms include the following: Cayenne Dong quai Siberian ginseng Pulsatilla Raspberry leaves St. John's wort
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THE IMPACT OF PMDD:
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- The burden of PMDD may be miss-perceived as less severe because it affects only a subset of women and not all the time - However, both tangible and intangible costs are present
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Yang et al (2008)
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- The adverse effects of PMDD on health-related quality of life have been shown to be greater than chronic back pain, comparable to debilitating conditions, such as osteoarthritis and rheumatoid arthritis
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Campagne and Campagne (2007) (P.4)
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"More women and their families are affected by the physical and psychological irregularities due to premenstrual symptoms than by any other condition"
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Stoddard et al (2007)
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- Women have between 400 and 500 menstrual cycles over their reproductive years, and since premenstrual distress symptoms peak during the 4-7 days prior to menses, consistently symptomatic women may spend from 4-10 years of their lives in a state of compromised physical functioning and/or psychological well-being
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Direct Costs
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- There are both direct and indirect costs associated with PMDD - Direct costs include healthcare, such as visits to the doctor, referrals to specialists, tests and treatment - Borenstein et al (2003) estimated over $500 over 2 years
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Indirect Costs
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- Indirect costs on work productivity and absenteeism - Higher rates of these during a womens difficult PMDD premenstural phase are being consistently shown accross different countries - Borensteind et al (2007) found significantly higher levels of absence and decreased work productivity in women with severe PMS symptoms compared with women with no/mild symptoms - Heinemann et al (2010) also found higher absence rates and reduced productivity across samples of different nationalities
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Financial Burden of PMDD
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- Borenstein et al (2005) found the annual financial burden of absenteeism and decreased productivity while at work resulted in $4333 US dollars lost per patient - However, more likely to be higher if we take into account turnover and women giving up on careers - Wider social and economic consequences and implications - Some countries and organisations even give 'Menstrual Leave'
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Conclusion
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- PMDD is a significant disorder that can have debilitating effects on patients and those around them - Significant direct and indirect costs - Impact on the workplace can be high, which may have serious known-on effects on the economy and society - Need more research on treatments, including non-pharmacological to give patients more choice - More research is needed to understand underlying causes of PMDD, which may in turn facilitate diagnosis and treatment - Need to provide more awareness to the general population and specifically employing organisations to help deal with female employees who may have PMDD
