Premenstrual Dysphoric Disorder

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:
  • Desquamation Desquamation Staphylococcal Scalded Skin Syndrome (SSSS): shedding of the endometrial lining ( 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) 
  • Proliferative phase Proliferative phase Menstrual Cycle: endometrial proliferation with straight, tubular glands
  • Secretory phase Secretory phase Menstrual Cycle: preparation of the spiral arteries Spiral arteries Placenta, Umbilical Cord, and Amniotic Cavity and endometrial glands for potential oocyte implantation Implantation Endometrial implantation of embryo, mammalian at the blastocyst stage. Fertilization and First Week

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

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.

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:
  • Serotonergic antidepressants are preferred pharmacologic therapy.
    • Selective 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 reuptake inhibitor ( SSRIs SSRIs Serotonin Reuptake Inhibitors and Similar Antidepressants): citalopram Citalopram A furancarbonitrile that is one of the serotonin uptake inhibitors used as an antidepressant. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia in preference to tricyclic antidepressants, which aggravate dyskinesia. Serotonin Reuptake Inhibitors and Similar Antidepressants, escitalopram Escitalopram Serotonin Reuptake Inhibitors and Similar Antidepressants, fluoxetine Fluoxetine The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. Serotonin Reuptake Inhibitors and Similar Antidepressants, sertraline Sertraline A selective serotonin uptake inhibitor that is used in the treatment of depression. Serotonin Reuptake Inhibitors and Similar Antidepressants
    • 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– norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS reuptake inhibitor ( SNRIs SNRIs Serotonin Reuptake Inhibitors and Similar Antidepressants): venlafaxine Venlafaxine A cyclohexanol and phenylethylamine derivative that functions as a serotonin and noradrenaline reuptake inhibitor (SNRI) and is used as an antidepressant agent. Serotonin Reuptake Inhibitors and Similar Antidepressants, duloxetine Duloxetine A thiophene derivative and selective neurotransmitter uptake inhibitor for serotonin and noradrenaline (SNRI). It is an antidepressant agent and anxiolytic, and is also used for the treatment of pain in patients with diabetes mellitus and fibromyalgia. Serotonin Reuptake Inhibitors and Similar Antidepressants
  • Hormonal interventions:
    • Oral contraceptives 
    • Gonadotropin-releasing hormone Gonadotropin-releasing hormone A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, luteinizing hormone and follicle stimulating hormone. Gnrh is produced by neurons in the septum preoptic area of the hypothalamus and released into the pituitary portal blood, leading to stimulation of gonadotrophs in the anterior pituitary gland. Puberty (GnRH) agonist
  • Dietary supplements and vitamins 
• 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 Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder 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 Abdominal Pain Acute Abdomen. 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.