Premenstrual Dysphoric Disorder

Premenstrual dysphoric disorder (PMDD) refers to a group of mood, somatic, and behavioral symptoms that follow a cyclical pattern experienced by some women prior to menstruation. Unlike premenstrual syndrome (PMS), PMDD is characterized by significant distress and/or functional impairment. Diagnosis is made clinically with history and physical exam. Management is 2-fold: via lifestyle modification and pharmacotherapy with serotonin reuptake inhibitors Serotonin Reuptake Inhibitors Antidepressants encompass several drug classes and are used to treat individuals with depression, anxiety, and psychiatric conditions, as well as those with chronic pain and symptoms of menopause. Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and many other drugs in a class of their own. Serotonin Reuptake Inhibitors and Similar Antidepressant Medications or oral contraceptives.

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Overview

Definition

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS) characterized by a mixture of behavioral, affective, and somatic symptoms that recur with menses.  Unlike PMS, PMDD is characterized by symptoms of anger, irritability, and internal tension.

Epidemiology

  • 5–8% of women suffer from symptoms of PMS
  • Approximately 3%–8% of women with PMS are also estimated to meet criteria for PMDD.
  • Many women (roughly 80%) report ≥ 1 physical or psychiatric symptom during menses that do not cause significant impairment.

Risk factors

  • History of traumatic events
  • Comorbid anxiety disorders
  • Lower education
  • Smoking 
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity 

Pathophysiology

Normal physiology

The menstrual cycle Menstrual cycle The menstrual cycle is the cyclic pattern of hormonal and tissular activity that prepares a suitable uterine environment for the fertilization and implantation of an ovum. The menstrual cycle involves both an endometrial and ovarian cycle that are dependent on one another for proper functioning. There are 2 phases of the ovarian cycle and 3 phases of the endometrial cycle. Menstrual Cycle is divided into 2 hormonally regulated phases: ovarian and endometrial.

  • Average adult menstrual cycle Menstrual cycle The menstrual cycle is the cyclic pattern of hormonal and tissular activity that prepares a suitable uterine environment for the fertilization and implantation of an ovum. The menstrual cycle involves both an endometrial and ovarian cycle that are dependent on one another for proper functioning. There are 2 phases of the ovarian cycle and 3 phases of the endometrial cycle. Menstrual Cycle: 28–35 days
  • Cycle intervals usually remain consistent until perimenopause, when follicular phases become shorter and more frequent.
  • Ovarian phases:
    • Follicular phase:
      • Spans from menses onset (day 1) to the day before the surge of luteinizing (LH) leading to ovulation
      • Length: 14–21 days
    • Luteal phase
      • Spans from the day of LH surge until the onset of the next menses
      • Length: 15 days
  • Endometrial phases:
    • Desquamation: shedding of the endometrial lining (menses) 
    • Proliferative phase: endometrial proliferation with straight, tubular glands
    • Secretory phase: preparation of the spiral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries and endometrial glands for potential oocyte implantation

Pathophysiology

  • The exact pathophysiologic mechanism of PMDD is unknown. 
  • Variables suspected to play a part in the pathophysiology of PMDD: 
    • Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics
    • Differences in brain function and structure
    • History of past trauma 
    • Fluctuations of levels of progesterone, estrogen, brain-derived neurotrophic factor, and serotonin
Normal physiology of the menstrual cycle

Normal physiology of the menstrual cycle Menstrual cycle The menstrual cycle is the cyclic pattern of hormonal and tissular activity that prepares a suitable uterine environment for the fertilization and implantation of an ovum. The menstrual cycle involves both an endometrial and ovarian cycle that are dependent on one another for proper functioning. There are 2 phases of the ovarian cycle and 3 phases of the endometrial cycle. Menstrual Cycle:
A diagram showing the correlation between the ovarian cycle and the endometrial cycle

Image by Lecturio.

Clinical Presentation

The symptoms of PMS can be both physical and behavioral.

  • Timing of symptom presentation:
    • Symptoms worsen approximately 5 days before start of menses.
    • Symptoms improve within a few days after onset of menses.
    • Symptoms resolve after menses.
    • The following symptoms must be present for ≥ 2 consecutive menstrual cycles.
Table: Affective symptoms of PMDD
Symptoms Woman’s description
Lability of affect/mood Sudden sadness, rapid mood swings, increased tearfulness
Irritability, frustration, rise in interpersonal conflicts Less able to control anger and may become more confrontational
Depression Self-doubt, negative thoughts, feelings of hopelessness
Anxiety or tension Feeling of being “on the edge”
Table: Behavioral or cognitive symptoms of PMDD
Symptoms Woman’s description
Decreased interest in daily activities (anhedonia) No longer finds joy or pleasure in hobbies, school, work, social circle
Impairments in concentration Decreased ability to remain focused through work, conversations, reading
Decreased energy or increased fatigue Reports being constantly tired or “I don’t want to get out of bed.”
Changes in appetite Food cravings, overeating
Sleep Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of Sleep disturbances Increased sleep (hypersomnia) or difficulty with sleep ( insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia)
Feeling of being out of control or overwhelmed “I can’t do this anymore.”
Somatic symptoms Tenderness or swelling of the breast, joint or muscle pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, sense of feeling “bloated,” weight gain
Table: Distinction between PMS and PMDD
PMS PMDD
Duration of symptoms Symptoms present immediately prior to menstruation and include fatigue, bloating, irritability, depression, and end immediately after menses starts Include mood and behavior changes that are present almost daily, including trouble functioning at home and work and end within a few days after menses starts
Confirmation of diagnosis Symptoms should be present 5 days before the onset of menstruation for 3 consecutive menstrual cycles Symptoms should typically be present 7 days before the onset of menses for most of the menstrual cycles over a period of 1 year
Interfering with daily activities Mildly Extremely

Diagnosis

  • Clinical diagnostic criteria 
    • ≥ 5 of the symptoms listed in the tables must be present.
    • Symptoms start in the days immediately prior to onset of menses, improve within a few days after start of menses, then resolve within a week after menses. 
    • Affective symptoms (as per 1st table) 
      • ≥ 1 of the 4 must be present
      • Lability of affect, increased irritability, depression, anxiety or tension
    • Behavioral or cognitive symptoms (as per 2nd table) 
      • ≥ 1 of the following must be present: 
        • Anhedonia, difficulty concentrating, fatigue, change in appetite, sleep disturbance, sense of being overwhelmed, somatic symptoms
  • A detailed medical history and physical exam to meet diagnostic criteria is sufficient. 
  • Imaging and laboratory testing may be indicated to rule out alternative diagnoses but are not necessary.
  • Diary of symptoms compiled by woman and prospective questionnaires also have diagnostic value.

Management

  • Pharmacologic approach:
    • Serotonergic antidepressants are preferred pharmacologic therapy.
      • Selective serotonin reuptake inhibitor (SSRIs): citalopram, escitalopram, fluoxetine, sertraline
      • Serotonin–norepinephrine reuptake inhibitor (SNRIs): venlafaxine
    • Hormonal interventions: 
      • Oral contraceptives 
      • Gonadotropin-releasing hormone (GnRH) agonist
    • Dietary supplements and vitamins 
  • Lifestyle changes:
    • Physical activity: exercise
    • Dietary changes: healthy diet
    • Avoid triggers: smoking, alcohol, stress
  • CBT:
    • Mindfulness-based exercises as well as CBT based on acceptance are linked with reduction of symptoms.
    • Thought to be helpful in treating disruptive mood-related changes

Differential Diagnosis

  • Anxiety disorders: group of psychiatric conditions exhibiting various symptoms, including mood changes, irritability, fatigue, and lack of concentration. The symptom of anxiety can be provoked by any triggering event. The anxiety symptoms can present as generalized anxiety disorder Generalized anxiety disorder Generalized anxiety disorder (GAD) is a common mental condition defined by excessive, uncontrollable worrying causing distress and occurring frequently for at least 6 months. Generalized anxiety disorder is more common in women. Clinical presentation includes fatigue, low concentration, restlessness, irritability, and sleep disturbance. Generalized Anxiety Disorder (GAD), as panic disorders, or as a part of major depression or premenstrual syndrome in women. Diagnosis is made clinically, and 1st-line management is a combination of pharmacotherapy (SSRI) and CBT. 
  • Thyroid disorders: Both hyperthyroidism Hyperthyroidism Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves' disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Thyrotoxicosis and Hyperthyroidism and hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism may have mood changes with a constellation of various somatic symptoms. Diagnosis is made via thyroid function tests, and ultrasonography may be required in select cases. Management is with supplementation of thyroid hormone in hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism and suppression of thyroid activity in hyperthyroidism Hyperthyroidism Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves' disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Thyrotoxicosis and Hyperthyroidism.
  • Irritable bowel syndrome Irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome ( IBS IBS Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome): functional disorder characterized by GI symptoms with altered bowel habits and associated abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain. This syndrome is very commonly seen in women, in whom the symptoms may occur before the menstrual cycle Menstrual cycle The menstrual cycle is the cyclic pattern of hormonal and tissular activity that prepares a suitable uterine environment for the fertilization and implantation of an ovum. The menstrual cycle involves both an endometrial and ovarian cycle that are dependent on one another for proper functioning. There are 2 phases of the ovarian cycle and 3 phases of the endometrial cycle. Menstrual Cycle. Mood changes can coexist with these symptoms. Irritable bowel syndrome Irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome is a diagnosis of exclusion, and management is with dietary modification and symptom control.

References

  1. Raffi, E. (2018). Diagnosis etiology, and treatment of premenstrual dysphoric disorder. DeckerMed Medicine. Retrieved September 30, 2021, from https://doi.org/10.2310/PSYCH.13018
  2. Hofmeister, S., Bodden, S. (2016). Premenstrual syndrome and premenstrual dysphoric disorder. American Family Physician 94.3:236–240.
  3. Pearlstein, T., Steiner, M. (2012). Premenstrual dysphoric disorder: burden of illness and treatment update. Focus 10(1):90–101.
  4. Yonkers, K. A., O’Brien, P. S., Eriksson, E. (2008). Premenstrual syndrome. Lancet 371:1200–1210. https://doi.org/10.1016/s0140-6736(08)60527-9
  5. Kwan, I., Onwude, J. L. (2015). Premenstrual syndrome. BMJ Clinical Evidence 2015:0806. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548199/

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