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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 Menstruation The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle. 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 Antidepressants or oral contraceptives.

Last updated: Nov 14, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS) characterized by a mixture of behavioral, affective, and somatic symptoms Somatic symptoms Major Depressive Disorder that recur with menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle.  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 Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle that do not cause significant impairment.

Risk factors

  • History of traumatic events
  • Comorbid anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder disorders
  • Lower education
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases 
  • 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 Perimenopause The transitional period before and after menopause. Perimenopausal symptoms are associated with irregular menstrual cycle and widely fluctuated hormone levels. They may appear 6 years before menopause and subside 2 to 5 years after menopause. Menopause, when follicular phases become shorter and more frequent.
  • Ovarian phases:
    • Follicular phase Follicular phase The period of the menstrual cycle representing follicular growth, increase in ovarian estrogen (estrogens) production, and epithelial proliferation of the endometrium. Follicular phase begins with the onset of menstruation and ends with ovulation. Menstrual Cycle:
      • Spans from menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle onset (day 1) to the day before the surge of luteinizing ( LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle) leading to ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle
      • Length: 14–21 days
    • Luteal phase Luteal phase The period in the menstrual cycle that follows ovulation, characterized by the development of corpus luteum, increase in progesterone production by the ovary and secretion by the glandular epithelium of the endometrium. The luteal phase begins with ovulation and ends with the onset of menstruation. Menstrual Cycle
      • Spans from the day of LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle surge until the onset of the next menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle
      • Length: 15 days
  • Endometrial phases:

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 Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification function and structure
    • History of past trauma 
    • Fluctuations of levels of:
      • Progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones
      • Estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy
      • Brain-derived neurotrophic factor
      • Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS
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 Correlation Determination of whether or not two variables are correlated. This means to study whether an increase or decrease in one variable corresponds to an increase or decrease in the other variable. Causality, Validity, and Reliability 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 Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle.
    • Symptoms improve within a few days after onset of menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle.
    • Symptoms resolve after menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle.
    • 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 Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder 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 Anhedonia Inability to experience pleasure due to impairment or dysfunction of normal psychological and neurobiological mechanisms. It is a symptom of many psychotic disorders (e.g., depressive disorder, major; and schizophrenia). Schizophrenia) 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 Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia Reports being constantly tired or “I don’t want to get out of bed.”
Changes in appetite Food cravings, overeating
Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disturbances Increased sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep ( hypersomnia Hypersomnia Disorders characterized by hypersomnolence during normal waking hours that may impair cognitive functioning. Subtypes include primary hypersomnia disorders (e.g., idiopathic hypersomnolence; narcolepsy; and kleine-levin syndrome) and secondary hypersomnia disorders where excessive somnolence can be attributed to a known cause (e.g., drug affect, mental disorders, and sleep apnea syndrome). Whipple’s Disease) or difficulty with sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of 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 Somatic symptoms Major Depressive Disorder Tenderness or swelling Swelling Inflammation of the breast, joint or muscle pain Muscle Pain Ion Channel Myopathy, sense of feeling “bloated,” weight gain
Table: Distinction between PMS and PMDD
PMS PMDD
Duration of symptoms Symptoms present immediately prior to menstruation Menstruation The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle and include fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, bloating Bloating Constipation, irritability, depression, and end immediately after menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle 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 Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle starts
Confirmation of diagnosis Symptoms should be present 5 days before the onset of menstruation Menstruation The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle for 3 consecutive menstrual cycles Symptoms should typically be present 7 days before the onset of menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle 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 Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle, improve within a few days after start of menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle, then resolve within a week after menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle
    • ≥ 1 of the following 4 affective symptoms must be present (as per the 1st table): 
      • Lability of affect
      • Increased irritability
      • Depression
      • Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder or tension
    • ≥ 1 of the following behavioral or cognitive symptoms must be present (as per 2nd table):
      • Anhedonia Anhedonia Inability to experience pleasure due to impairment or dysfunction of normal psychological and neurobiological mechanisms. It is a symptom of many psychotic disorders (e.g., depressive disorder, major; and schizophrenia). Schizophrenia
      • Difficulty concentrating
      • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
      • Change in appetite
      • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disturbance
      • Sense of being overwhelmed
      • Somatic symptoms Somatic symptoms Major Depressive Disorder
  • 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:
  • Lifestyle changes:
    • Physical activity: exercise
    • Dietary changes: healthy diet
    • Avoid triggers: smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases, 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 Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder disorders: group of psychiatric conditions exhibiting various symptoms, including mood changes, irritability, fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, and lack of concentration. The symptom of anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder can be provoked by any triggering event. The anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder 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 GAD 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), 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 Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy disorders: Both hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. 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 Somatic symptoms Major Depressive Disorder. Diagnosis is made via thyroid function tests Thyroid Function Tests Blood tests used to evaluate the functioning of the thyroid gland. Ion Channel Myopathy, and ultrasonography may be required in select cases. Management is with supplementation of thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy 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 Suppression Defense Mechanisms of thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy activity in hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. 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 An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. 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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